Document ID: FDA-2013-N-0067-0001
Agency: fda
Document Type: Proposed Rule
Title: Infant Formula: The Addition of Minimum and Maximum Levels of Selenium to Infant Formula and Related Labeling Requirements
Posted Date: 2013-04-16T04:00Z

[Federal Register Volume 78, Number 73 (Tuesday, April 16, 2013)]
[Proposed Rules]
[Pages 22442-22451]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 2013-08855]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 107

[Docket No. FDA-2013-N-0067]

Infant Formula: The Addition of Minimum and Maximum Levels of 
Selenium to Infant Formula and Related Labeling Requirements

AGENCY: Food and Drug Administration.

ACTION: Proposed rule.

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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the regulations on nutrient specifications and labeling for infant 
formula to add the mineral selenium to the list of required nutrients 
and to establish minimum and maximum levels of selenium in infant 
formula.

DATES: Submit either electronic or written comments on the proposed 
rule by July 1, 2013. Submit comments on information collection issues 
under the Paperwork Reduction Act of 1995 by May 16, 2013, (see the 
``Paperwork Reduction Act of 1995'' section of this document).

ADDRESSES: You may submit comments, identified by Docket No. FDA-2013-
N-0067, by any of the following methods, except that comments on 
information collection issues under the Paperwork Reduction Act of 1995 
must be submitted to the Office of Information and Regulatory Affairs, 
Office of Management and Budget (OMB) (see the ``Paperwork Reduction 
Act of 1995'' section of this document):

Electronic Submissions

    Submit electronic comments in the following way:
     Federal eRulemaking Portal: http://www.regulations.gov. 
Follow the instructions for submitting comments.

Written Submissions

    Submit written submissions in the following way:
     Mail/Hand delivery/Courier (for paper or CD-ROM 
submissions): Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.
    Instructions: All submissions received must include the Agency name 
and Docket No. FDA-2013-N-0067 for this rulemaking. All comments 
received may be posted without change to http://www.regulations.gov, 
including any personal information provided. For additional information 
on submitting comments, see the ``How Do You Submit Comments on This 
Rule?'' 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.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts or go to the Division of 
Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: With regard to the proposed rule: 
Benson M. Silverman, Center for Food Safety and Applied Nutrition (HFS-
850), Food and Drug Administration, 5100 Paint Branch Pkwy, College 
Park, MD 20740, 240-402-1450.
    With regard to the information collection issues: Domini Bean, 
Office of Information Management, Food and Drug Administration, 1350 
Piccard Dr., PI50-400T, Rockville, MD 20850, domini.bean@fda.hhs.gov.

SUPPLEMENTARY INFORMATION:

I. What is the background of this proposed rule?

    Section 412(i) of the Federal Food, Drug, and Cosmetic Act (the 
FD&C Act) (21 U.S.C. 350a(i)) establishes requirements for the nutrient 
content of infant formulas. Under section 412(i)(2) of the FD&C Act, 
the Secretary of Health and Human Services (the Secretary) is 
authorized to revise the list of required nutrients and the required 
level for any required nutrient, which authority has been delegated to 
the Commissioner of Food and Drugs (the Commissioner). The table in 
section 412(i) of the FD&C Act and FDA regulations, 21 CFR 107.100, 
specify that infant formulas must contain 29 nutrients; minimum levels 
for each nutrient and maximum levels for 9 of the nutrients are also 
specified.
    At the time FDA established nutrient specifications for infant 
formula, selenium was not recognized as an essential nutrient and was 
not one of the nutrients required by statute in infant formula. As 
explained in detail in this document, selenium has subsequently been 
recognized as an essential nutrient. Therefore, we are proposing to 
amend the nutrient specifications for infant

[[Page 22443]]

formula in Sec.  107.100 to include selenium as a required nutrient and 
to establish minimum and maximum values for selenium. We are also 
proposing to amend the labeling requirements for infant formula in 21 
CFR 107.10 to add selenium to the list of nutrients along with the 
requirement to list the amount of selenium per 100 kilocalories in the 
formula.
    Selenium is an essential trace element for humans that functions 
largely through an association with proteins known as selenoproteins. 
The known biological functions of selenium include defense against 
oxidative stress, regulation of thyroid hormone action, and regulation 
of the oxidation/reduction status of vitamin C and other molecules.
    Plant foods are the major dietary sources of selenium although 
selenium is also found in some meats, seafood, and nuts. The selenium 
content of a food depends on the selenium content of the soil where the 
plant was grown or where the animal was raised. In the United States, 
food distribution patterns across the country help prevent people 
living in geographic areas with low-selenium levels in the soil from 
having low dietary selenium intakes. Keshan disease, a cardiomyopathy 
that occurs almost exclusively in children, has been linked to selenium 
deficiency. Keshan disease occurs in areas of China where the 
population has severe selenium deficiency. Chronic selenium toxicity 
(selenosis) has also been observed in persons consuming diets 
containing high levels of selenium. Reported characteristics include 
hair and nail brittleness and loss, gastrointestinal upsets, skin rash, 
garlic breath odor, fatigue, irritability, and nervous system 
abnormalities. Acute selenium toxicity is rare and the few reports in 
the literature of acute fatal or near fatal selenium poisoning have 
occurred because of accidental or suicidal ingestion of selenium (Ref. 
1).
    In the United States, selenium is not routinely added to food. An 
exception is infant formula, a food that is intended to be the sole 
source of nutrition for infants and therefore, must provide sufficient 
amounts of all nutrients essential for infants. In 1989, the Food and 
Nutrition Board of the National Research Council established a 
Recommended Dietary Allowance (RDA) for selenium for infants 0 to 6 
months of age of 10.0 micrograms per day ([mu]g/day), a level 
extrapolated from adult values on the basis of body weight and with a 
factor allowed for growth (Ref. 2). Although selenium is not currently 
required in infant formula by Sec.  107.100, all U.S. manufacturers are 
adding selenium to their infant formulas. Based on labeling 
information, currently marketed infant formulas contain 1.8 [mu]g to 
3.0 [mu]g selenium per 100 kilocalorie (kcal) of formula.

II. What levels of selenium are we proposing for infant formula?

    As discussed in more detail in this document, we are proposing 2.0 
[mu]g selenium/100 kcal as the minimum level for selenium in infant 
formulas and 7.0 [mu]g/100 kcal as the maximum level of selenium in 
infant formulas

III. What scientific evidence did we consider for the proposed 
requirement to add selenium to infant formulas?

    In order to add a selenium requirement and to establish minimum and 
maximum levels of selenium in infant formula, we first identified and 
reviewed three relevant technical reports on recommended nutrient 
levels for formulas for term infants and nutrient needs of healthy term 
infants: (1) The Life Sciences Research Office (LSRO) report 
``Assessment of Nutrient Requirements for Infant Formulas'' (Ref. 3); 
(2) ``Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and 
Carotenoids'' (Ref. 1); and (3) ``Global Standard for the Composition 
of Infant Formula: Recommendations of an ESPGHAN Coordinated 
International Expert Group'' (Ref. 4). These reports are referred to as 
the LSRO report, the Institute of Medicine (IOM) report, and the 
European Society on Pediatric Gastroenterology, Hepatology, and 
Nutrition (ESPGHAN) report, respectively, in the remainder of this 
proposal. We also searched the published scientific literature from 
1998 through 2012 for published studies not included in these reports 
or not identified in a 2008 published study by Daniels et al. (Ref. 5). 
(The Daniels et al. study is discussed in this section of the 
document.)

A. Available Evidence for Setting a Minimum Level of Selenium in Infant 
Formula

1. LSRO Report
    In 1998, Raiten et al. published a report summarizing the 
scientific literature on the nutrient needs of healthy term infants, 
with an emphasis on research studies published since 1983 (Ref. 3). The 
report was prepared for FDA's Center for Food Safety and Applied 
Nutrition and Health Canada's Health Protection Branch by the LSRO in 
consultation with expert scientists and professional organizations 
involved in the field of infant nutrition. The goal of the 
deliberations of this LSRO Expert Panel was to provide recommendations 
for nutrient content of infant formulas that could serve as the sole 
source of nutrition for term infants throughout the first year of life.
    On the basis of the evidence for the dietary essentiality of 
selenium, the LSRO Expert Panel recommended that selenium be included 
as a required nutrient in infant formula. The Panel also recommended a 
minimum selenium content of 1.5 [mu]g/100 kcal (10.0 [mu]g/liter (L)), 
which) and a maximum level of 5.0 [mu]g/100 kcal (33.5 [mu]g/L). The 
minimum value approximated the estimated value for the mean minus one 
standard deviation (SD) for the selenium concentration in human milk in 
countries in which selenium deficiency has not been recognized in 
breast-fed infants. This recommended minimum level would provide an 
estimated 7.5 [mu]g/day of selenium for young infants exclusively fed 
infant formula,\1\ an amount below the 1989 RDA (10.0 [mu]g/day). The 
LSRO Panel was aware that there were disparities between some of its 
recommendations for nutrient levels in infant formulas and the 1989 
RDAs; however, the history of use for a large population in which 
selenium deficiency has not been reported was regarded as a reasonable 
basis for recommending a minimum value for selenium in infant formula.
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    \1\ This estimate is based on a calculation used to convert 
nutrient intake values (e.g., milligram (mg)/day) to formula 
nutrient content values (e.g., mg/100 kcal) (Raiten, et al., 1998; 
Koletzko, et al, 2006). The calculation is based on the following 
assumptions: (1) The mean intake of formulas for infants 0 to 6 
months of age is 750 milliliter (ml)/day; (2) a representative body 
weight for infants over this period is 5 kilogram (kg); and (3) a 
representative caloric intake of infants over this period is 500 
kcal/day (or 100 kcal/kg/day).
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2. IOM Report
    In 2000, the IOM published Dietary Reference Intakes (DRI) for 
selenium. The DRI concept evolved from the Recommended Dietary 
Allowances reports that have been published periodically since 1941 by 
the National Academies of Science. As described by the IOM (Ref. 1), 
the term Dietary Reference Intake encompasses three nutrient-based 
reference values in addition to the RDA. The RDA and the three 
nutrient-based reference values were described by the IOM as follows:
     The Recommended Dietary Allowance (RDA) is the average 
dietary intake level that is sufficient to meet the nutrient 
requirements of nearly all (97 to 98 percent) healthy individuals in a 
particular life stage and gender group.

[[Page 22444]]

The RDA is intended to be the goal for daily intake by individuals.
     The Estimated Average Requirement (EAR) is the daily 
intake value that is estimated to meet the requirement, as defined by 
the specified indicator of adequacy, in half of the healthy individuals 
in a life stage and gender group. The EAR is used to set the RDA. If 
the standard deviation (SD) of the EAR is available and the requirement 
for the nutrient is normally distributed, the RDA is defined as the EAR 
plus two SDs of the EAR.
     An Adequate Intake (AI) is established for a nutrient when 
sufficient scientific evidence is not available to calculate an EAR. An 
AI is based on experimentally-derived intake levels of approximations 
of observed mean nutrient intakes by a group of healthy people. The AI 
for children and adults is expected to meet or exceed the amount needed 
to maintain a defined nutritional state or exceed the amount needed to 
maintain a defined nutritional state or criterion of adequacy in 
essentially all members of a specific healthy population because it is 
set using healthy populations. Like the RDA, the AI is intended to be 
the goal for individual intake and it is intended to cover the needs of 
nearly all persons in a life stage group.
     The Tolerable Upper Intake Level (UL) is the highest daily 
intake level of a nutrient that is likely to pose no risk of adverse 
health effects in almost all individuals in a life stage group.
    At the time of its report, the IOM did not find sufficient evidence 
to calculate an EAR for selenium for infants during the first year of 
life and, therefore, did not have a basis to set an RDA for selenium 
for infants. For this reason, the IOM set an AI for selenium for 
infants 0 to 6 months of age, the age when the recommended sole source 
of nutrition is human milk, infant formula, or a combination of the 
two.
    The IOM's primary basis for deriving an AI for most nutrients for 
the first 6 months of life was the average intake by full term infants 
born to healthy, well-nourished mothers and exclusively fed human milk. 
To derive the AI values for infants ages 0 to 6 months of age, the mean 
intake of a nutrient was calculated based on the average concentration 
of the nutrient in human milk from 2 to 6 months of lactation, using 
agreed-upon values from several reported studies and an average volume 
of milk intake. To calculate the AI for selenium, IOM used the average 
concentration of selenium in human milk from mothers in the United 
States and Canada (18.0 [mu]g/L) and an intake of 0.78 L/day, as 
reported from differences in weights of full-term infants before and 
after feedings. A reference weight of 7 kg for infants 2 to 6 months of 
age, adapted from National Health and Nutrition Examination Survey 
(NHANES) III 1988-1994 data (Ref. 6), was used by the IOM to calculate 
the AI on a body weight basis. (Ref. 1). The IOM established a selenium 
AI of 15.0 [mu]g/day (approximately 2.1 [mu]g/kg body weight/day) for 
infants 0 to 6 months of age (IOM, 2000). Assuming a typical intake of 
100 kcal/kg/day for infants 0 to 6 months of age, this approximates a 
need for selenium, relative to energy consumption, of 2.1 [mu]g/100 
kcal.
3. ESPGHAN Report
    In 2005, an International Expert Group (IEG) coordinated by the 
Committee on Nutrition of the ESPGHAN prepared a report on nutrient 
levels in infant formula, based on scientific analysis and taking into 
account existing scientific reports on current infant formula nutrient 
content (Ref. 4). The report was prepared at the request of the Codex 
Committee on Nutrition and Foods for Special Dietary Uses for use by 
that Committee in revising the Codex Standard for Infant Formula and 
Formulas for Special Medical Purposes Intended for Infants (Codex Stan 
72-1981) (Ref. 7). The goal of establishing minimum and maximum 
nutrient values for the Codex standard was to ensure that infant 
formulas adhering to the Standard would be safe and would meet infants' 
normal nutritional requirements.
    The ESPGHAN IEG reported that their recommended minimum nutrient 
values were based on scientific evidence of the amounts needed to meet 
infants' nutritional requirements when such information was available. 
When scientific information was lacking, an established history of 
apparent safe use was taken into account. The IEG recommended a minimum 
selenium value of 1 [mu]g/100 kcal for infant formula and they 
indicated that the reported median selenium content of human milk and 
values set for infant reference nutrient intakes formed the basis for 
their recommendation. Further detail was not provided on how this 
information was used by the IEG in making their recommendation.
4. Recent Published Literature
    One recent report in the published scientific literature also 
provides important information on necessary infant selenium intake 
levels. Daniels, et al. reported the results of a randomized, double-
blinded dose-response study of healthy term infants fed infant formula 
containing selenium at three concentrations (6.0 [mu]g/liter, 13.0 
[mu]g/liter, or 21.0 [mu]g/liter) and a breast-fed reference group 
(Ref. 5). The concentrations of selenium in the study formulas 
correspond to 0.9 [mu]g/100 kcal (low selenium control), 1.9 [mu]g/100 
kcal, and 3.1 [mu]g/100 kcal, respectively. The mean concentration of 
selenium in breast milk reported in this study was 11.0 [mu]g/liter 
(1.6 [mu]g/100 kcal). Infants participating in the study consumed the 
assigned infant formula or breast milk as the sole source of nutrition 
from birth to 16 weeks of age.
    Consumption of formulas containing both of the higher levels of 
selenium (1.9 [mu]g/100 kcal and 3.1 [mu]g/100 kcal) resulted in 
changes in plasma and erythrocyte indicators of selenium status at the 
end of the study that did not differ statistically from each other or 
from the breast-fed control group. However, indicators of selenium 
status for all of these groups differed statistically from the plasma 
and erythrocyte indicators of selenium status in the infants fed the 
control formula containing only 0.9 [mu]g selenium/100 kcal. A dose-
related increase in urinary selenium excretion in the formula-fed 
groups was also reported. When infants consumed formulas containing 
selenium at levels of 1.9 [mu]g/100 kcal or 3.1 [mu]g/100 kcal, there 
were no statistically significant dose-related changes in plasma and 
erythrocyte indicators of selenium status. However, there was a 
statistically significant increase in urinary selenium excretion in the 
infants fed the formula containing 3.1 [mu]g/100 kcal compared to the 
infants fed the formula containing 1.9 [mu]g/100 kcal. This latter 
finding, in combination with the finding of no dose-related changes in 
the circulating indicators of selenium status, suggests that infants 
fed the formula containing a level of 1.9 [mu]g selenium/100 kcal 
received sufficient selenium to meet their nutritional needs and that 
by virtue of the body's homeostatic mechanisms, it would appear that 
much of the selenium intake above the level of 1.9 [mu]g selenium/100 
kcal was eliminated from the body.

B. Available Evidence for Setting a Maximum Level for Selenium in 
Infant Formula

1. LSRO Report
    The LSRO Expert Panel recommended a maximum selenium level for 
infant formula of 5.0 [mu]g/100 kcal (33.5 [mu]g/L) (Ref. 3). This 
recommendation was based on the upper limit of the range of selenium in 
human milk, which was considered to represent a history of use for a 
large population in which

[[Page 22445]]

selenium toxicity had not been reported. The LSRO report also indicated 
that, on a body weight basis, this level is far below the intake 
associated with the development of selenosis in adults.
2. IOM Report
    The IOM established an upper limit (UL) for selenium for infants 0 
to 6 months of age relying on data on the concentration of selenium in 
human milk, which is not associated with known adverse effects. The IOM 
calculated an UL of 47.0 [mu]g/day or approximately 7.0 [mu]g/kg body 
weight/day for infants 0 to 6 months of age, which approximates 7.0 
[mu]g/100 kcal.
3. ESPGHAN Report
    The ESPGHAN IEG recommended a maximum level of 9 [mu]g/100 kcal for 
selenium in infant formula. The IEG based their recommendations for 
maximum nutrient values on scientific evidence regarding the absence of 
adverse effects, when such information was available. When scientific 
information was lacking, an established history of apparent safe use 
was taken into account. Further detail was not provided on how this 
information was used by the IEG in making its recommendation.

IV. Which products are subject to this proposed rule?

    Products that meet the statutory definition of ``infant formula'' 
in section 201(z) of the FD&C Act (21 U.S.C. 321(z)) (``a food which 
purports to be or is represented for special dietary use solely as a 
food for infants by reason of its simulation of human milk or its 
suitability as a complete or partial substitute for human milk'') are 
subject to this proposed rule.

V. What does this proposed rule do?

    This proposed rule, if finalized, will add selenium to the list of 
required nutrients for infant formulas and establish minimum and 
maximum levels of selenium in FDA's nutrient specifications regulations 
for infant formulas under Sec.  107.100(a). In addition, the proposed 
rule would add selenium to the list of nutrients that must be listed in 
the table of nutrition information required on infant formula labeling 
by Sec.  107.10(a)(2).

A. Revision to Sec.  107.100(a) Nutrient Specifications

    We are proposing to mandate that selenium be added to infant 
formula by requiring that this mineral be listed in the table of 
nutrients for infant formulas in Sec.  107.100(a). We are also 
proposing to establish minimum and maximum levels for selenium in 
infant formula because evidence exists for both deficiency and toxicity 
of selenium, and there is no room for error in production of a food 
that serves as the sole source of nutrition for infants.
1. Proposed Minimum Level of Selenium in Infant Formulas
    After considering the scientific reports discussed previously in 
this document and evidence published by Daniels, et al. after those 
reports were completed, we are proposing 2.0 [mu]g selenium/100 kcal as 
the minimum level for selenium in infant formulas. This proposed 
minimum level is based on the IOM's AI for selenium for infants 0 to 6 
months of age (2.1 [mu]g/day) (Ref. 1) and the level suggested by the 
data in the study by Daniels, et al. (1.9 [mu]g/100 kcal) (Ref. 5), 
rounded to the nearest whole microgram. As noted, the Daniels, et al. 
study demonstrated that infants who consumed infant formula containing 
1.9 [mu]g selenium/100 kcal had plasma and erythrocyte indicators of 
selenium status that were statistically higher than those of infants 
consuming formula containing less selenium (0.9 [mu]g/100 kcal) but 
these levels did not differ from those of infants consuming infant 
formula containing more selenium (3.1 [mu]g/100 kcal). Infants 
consuming the formula containing 3.1 [mu]g/100 kcal of selenium also 
had significantly higher urinary excretion of selenium. In the absence 
of statistically significant changes in plasma and erythrocyte 
indicators of selenium status, the substantially higher urinary 
excretion of selenium of the infants fed the 3.1 [mu]g selenium formula 
compared to that of the infants fed the 1.9 [mu]g selenium formula, 
suggests that a selenium intake of 3.1 [mu]g/100 kcal is likely to be 
greater than the amount needed to meet an infant's nutritional needs. 
Thus, FDA tentatively concludes that 2.0 [mu]g selenium/100 kcal is an 
appropriate required minimum for selenium in infant formulas.
    We also propose to correct a typographical error in the table that 
appears in Sec.  107.100(a). In the second column of that table, each 
abbreviation for ditto (``do'') will now be followed by a period.
2. Proposed Maximum Level of Selenium in Infant Formulas
    FDA is also proposing to set a maximum level for selenium in infant 
formula of 7.0 [mu]g/100 kcal. This level is based on the UL for 
infants 0 to 6 months of age established by the IOM (Ref. 1), and 
defined as highest level of daily nutrient intake that is likely to 
pose no risk of adverse health effects in the population of interest. 
FDA is relying on the IOM's recommendation because the IOM report was 
the most transparent in terms of the basis for its recommended UL. 
Also, unlike the minimum level, there is no study that provides direct 
evidence to establish a maximum level and thus, in proposing a maximum 
level, the agency must rely on a recommendation for an intake level 
that is likely to pose no risk of adverse health effects.
3. Comments Specifically Requested
    We find that there is scientific evidence sufficient to support the 
minimum proposed level of 2.0 [mu]g selenium/100 kcal and the proposed 
maximum level of 7.0 ug selenium/100 kcal, although there is less 
evidence directly applicable to the proposed maximum level. While we 
are interested in comments regarding the proposed minimum level for 
selenium, we are particularly interested in comments regarding the 
proposed maximum level of 7.0 [mu]g selenium/100 kcal, including 
whether such a maximum level is needed and the scientific data or 
information that form the basis of any comments.
    Although, in our judgment, it will be feasible for formula 
manufacturers to achieve consistent production of infant formulas with 
selenium levels that are at or above the proposed minimum level of 2.0 
[mu]g/100 kcal while not exceeding the proposed maximum level of 7.0 
[mu]g/100 kcal, we specifically request comments about whether the 
proposed minimum and maximum selenium levels provide sufficient 
flexibility and can be achieved from a practical manufacturing 
standpoint. In addition, because unduly high levels of nutrients should 
be avoided in products that serve as the sole source of nutrients for 
infants, a population that is particularly vulnerable to nutritional 
inadequacies and excesses, we are also particularly interested in 
receiving comments about available means to ensure that nutrient levels 
in infant formulas, including selenium, are not excessive.

B. Revision to Sec.  107.10(a)(2) Nutrient Information

    We are proposing to add selenium to the statement of the amounts of 
nutrients required for infant formula labeling in Sec.  107.10(a)(2). 
This additional mineral would be required to be listed between iodine 
and sodium, as directed by Sec.  107.10(b)(5).

VI. What is the legal authority for this proposed rule?

    Section 412(i) of the FD&C Act contains a table of nutrients 
(including

[[Page 22446]]

minimum and, in some cases, maximum levels for such nutrients) that are 
required to be in an infant formula. Section 412(i)(2) of the FD&C Act 
authorizes the Secretary to revise the statutory table of nutrients and 
to revise the level of any required nutrient. The Secretary has 
delegated this authority to the Commissioner. In the Federal Register 
of October 31, 1985, FDA published a final rule revising the statutory 
table of nutrients, which was published as Sec.  107.100. This proposed 
rule, if finalized, would amend Sec.  107.100. Accordingly, the legal 
authority for the proposed revision to Sec.  107.100, which revises the 
statutory list of nutrients required for infant formula, is section 
412(i)(2) of the FD&C Act.
    Additionally, this proposed rule, if finalized, would require the 
addition of selenium to the statement of the amounts of nutrients 
required for infant formula labeling in Sec.  107.10(a)(2). As noted 
previously in this document, ``infant formula'' is defined as a food 
for ``special dietary use'' under section 201(z) of the FD&C Act. Under 
sections 403(j) and 701(e) of the FD&C Act (21 U.S.C. 343(j) and 21 
U.S.C. 371(e)), the Secretary, and by delegation the Commissioner, may 
prescribe regulations concerning the vitamin and mineral content of 
foods for special dietary uses, in order to fully inform purchasers as 
to the value of the food for such uses. As such, FDA has the authority 
to revise the statement of the amounts of nutrients required for infant 
formula labeling in Sec.  107.10(a)(2) under sections 201(z), 403(j), 
412(i), and 701(e) of the FD&C Act. When the Agency issues a final rule 
for the provisions in proposed Sec.  107.10(a)(2), it will provide an 
opportunity for filing objections and requests for a formal evidentiary 
public hearing under 21 CFR part 12.

VII. What is the environmental impact of this proposed rule?

    FDA has determined under 21 CFR 25.32(n) 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.

VIII. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed rule, if finalized, would 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, the Agency concludes that the proposed rule does not 
contain policies that have federalism implications as defined in the 
Executive order and, consequently, a federalism summary impact 
statement is not required.

IX. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866, Executive Order 13563, the Regulatory Flexibility Act (5 
U.S.C. 601-612), and the Unfunded Mandates Reform Act of 1995 (Pub. L. 
104-4). Executive Orders 12866 and 13563 direct 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). The Agency believes that this proposed rule is not a 
significant regulatory action as defined by Executive Order 12866.
    The Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. Because only one firm is affected by this rule, and 
it is considered large by Small Business Administration standards, the 
Agency proposes to certify that the final rule will not have a 
significant economic impact on a substantial number of small entities.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that Agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any 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 $136 million, using the most current (2010) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.

X. Regulatory Impact Analysis

A. Need for This Regulation

    FDA is proposing to amend its infant formula nutrient requirement 
regulations. If the proposed rule is finalized, infant formulas will be 
required to contain selenium at a level not less than 2.0 [mu]g and not 
more than 7.0 [mu]g for each 100 kilocalories of the infant formula in 
the form prepared for consumption as directed on the container. This 
regulation is needed because selenium is now recognized as an essential 
nutrient for humans.
    Additionally, if finalized, this proposed rule will require that 
infant formula manufacturers add selenium to the list of nutrients on 
infant formula labels, and to list the amount of selenium per 100 
kilocalories in the formula.
    Selenium is a trace mineral that is essential to good health but 
required only in small amounts. Selenium is incorporated into proteins 
to make selenoproteins, which are important antioxidant enzymes, the 
natural by-products of oxygen metabolism that may contribute to the 
development of chronic diseases such as cancer and heart disease. In 
most countries throughout the world, plant foods are major dietary 
sources of selenium. However, selenium is also found in some meats, 
seafood, and nuts. In the United States, food distribution patterns 
across the country help prevent people in geographic areas with low-
selenium levels in the soil from having low dietary selenium intakes. 
Food is not generally fortified with selenium in the United States, but 
an exception to this is infant formula.

B. Regulatory Options

    In formulating the analysis of this proposed rule, three options 
were analyzed: (1) No new regulatory action (baseline); (2) require the 
provisions of this proposed rule and make the provisions of the rule 
effective 180 days after publication; and (3) require the provisions of 
this proposed rule, but make the provisions of the rule effective 12 
months after publication.
    Option 1: No New Regulatory Action (Baseline)
    The first option is no new regulatory action. We include it here 
because OMB cost-benefit analysis guidelines recommend discussing 
statutory requirements that affect the selection of regulatory 
approaches. These guidelines also recommend analyzing the opportunity 
cost of legal constraints that prevent the selection of the regulatory 
action that best satisfies the philosophy and principles of Executive 
Order 12866. There are zero costs and benefits associated with this 
option, and it serves as the baseline against which other options will 
be measured for assessing costs and benefits.

[[Page 22447]]

    Option 2: Finalize the proposed rule and make the provisions 
effective 180 days after publication.

XI. Costs

    One cost of this proposal, if finalized, will be reformulation 
costs resulting from firms adding selenium to infant formulas in order 
to comply with this rule. Currently, there are five firms that produce 
infant formula in the United States. Of these firms, only one will need 
to add slightly more selenium to its infant formulas. Based on 
information provided by the infant formula industry, it appears that 
all other infant formula manufacturers already added selenium to their 
infant formula products at a level within the range identified by the 
proposed rule. Therefore, any reformulation cost of this proposal will 
come from a single firm adding slightly more selenium to its infant 
formula products that currently do not meet the proposed minimum level 
of 2.0 [mu]g/100 kcal.
    Table 1 of this document outlines low, medium, and high cost 
estimates based on a change in the formulation of infant formula. Costs 
are estimated using a reformulation model, developed under contract 
with Research Triangle Institute (RTI). This model provides estimates 
of the costs of reformulation of the range of food, dietary supplement, 
and cosmetic products under FDA's jurisdiction, including infant 
formulas, and has been adjusted to reflect 2012 dollars. In this model, 
the cost of the reformulation depends on the affected ingredient and 
the likely response of manufacturers. The cost per infant formula 
associated with reformulation is estimated to be a function of product 
research, product development, coordinating activities, startup and 
verification, and nutrient testing of finished product. To the extent 
that any of these activities is not necessary for adding selenium to an 
infant formula that already has selenium added, costs will be 
overestimated. Table 1 of this document presents total estimated low, 
medium, and high costs of reformulation for this proposed rule. The 
totals are based on the reformulation of 46 separate infant formulas 
manufactured by one firm, the current formulation of which would not 
meet the requirements of this rule, if finalized. Therefore, the total 
industry costs are each of the low, medium, and high costs multiplied 
by 46.

           Table 1--Estimation of First-Year Costs of Infant Formula Reformulation, per Infant Formula
----------------------------------------------------------------------------------------------------------------
                            Variable                                    Low           Medium           High
----------------------------------------------------------------------------------------------------------------
Product Research................................................          $1,685         $16,853         $33,706
Product Development.............................................           4,598          13,023          28,259
Coordinating Activities.........................................           2,938           8,818          14,690
Startup and Verification........................................           1,442           7,207          15,890
Nutrient Testing of the Finished Product........................              15              15              15
                                                                 -----------------------------------------------
    Total Per Formula...........................................          10,678          45,916          92,560
    Total Industry Cost of Reformulation (Cost x 46 infant               497,188       2,112,136       4,257,760
     formulas)..................................................
----------------------------------------------------------------------------------------------------------------

    Another component of the costs of this option is cost related to 
the relabeling of reformulated infant formula. The proposed rule 
requires infant formula manufacturers to include selenium in the 
nutrient content statement on containers of infant formula. All 
manufacturers currently disclose selenium in the nutrient list as 
specified under Sec.  107.10(b)(5). However, as noted previously in 
this document, one manufacturer would be required to add more selenium 
to its formulas under this proposal. Therefore, it is estimated that 
the same firm that would be required to add more selenium to its 
formulas under this proposal will also incur relabeling costs to comply 
with this proposed rule.
    Table 2 of this document outlines low, medium, and high cost 
estimates of relabeling based on a minor change to the infant formula 
label and an effective date of 180 days after publication. Costs are 
estimated using a relabeling model developed under contract by RTI. 
This model estimates the costs of relabeling food, dietary supplements, 
and cosmetic products under FDA's jurisdiction and these estimates have 
been adjusted to reflect 2012 dollars. In this model, relabeling costs 
depend on the type of change (major, minor, or extensive) and the 
effective date of the rule. This model estimates that longer periods of 
time before a rule becomes effective are associated with lower 
relabeling costs because any change is more likely to be able to be 
coordinated with a change in a label that may already be scheduled, and 
will diminish the need to, for example, purchase and apply stickers to 
packages affected by the change. The Agency acknowledges the 
uncertainty in this estimation and how it may specifically apply to the 
infant formula industry and requests comment regarding the extent to 
which the effective date is likely to affect the cost of compliance 
with this proposed rule.

             Table 2--Estimated First Year Relabeling Costs
------------------------------------------------------------------------
                     Low                         Medium         High
------------------------------------------------------------------------
$3,565,880..................................   $8,735,802   $23,619,959
------------------------------------------------------------------------

    The final component of cost is related to one firm assembling 
information for submission to the Agency related to the reformulated 
infant formulas, as required under section 412(d)(3) of the FD&C Act. 
The addition of more selenium constitutes a change in the formulation 
of these formulas that the Agency considers may affect whether the 
formulas are adulterated; therefore, we are including the submission of 
information about the change in the formulas before the first 
processing of such formulas as a cost.
    It is estimated that a scientist from one firm will spend 10 hours 
assembling the information to be submitted, which will address the 46 
reformulated infant formulas. This is estimated as a one-time cost. It 
is estimated that this scientist is paid a wage of $52.88; that is, 
$35.25 plus 50 percent overhead. Therefore, 10 hours x $52.88 = 
$528.80.

[[Page 22448]]

                                   Table 3--Summary of Total Cost of Option 1
----------------------------------------------------------------------------------------------------------------
                                             Low                         Medium                     High
----------------------------------------------------------------------------------------------------------------
Reformulation Cost............  $491,188....................  $2,112,136.................  $4,257,760.
First Year Relabeling Costs...  $3,467,560..................  $8,735,802.................  $23,619,959.
First Year Submission Costs...  $529........................  $529.......................  $529.
                               ---------------------------------------------------------------------------------
    Total Cost of Option 1....  $3.95 million...............  $10.85 million.............  $27.88 million.
----------------------------------------------------------------------------------------------------------------

As seen in table 3 of this document, the total cost of this option 
ranges from $3.95 million to $27.88 million, with the majority of cost 
coming from relabeling.

XII. Benefits

    The potential benefits from this proposed rule, if finalized, are 
any cases of selenium deficiency that are avoided as a result of infant 
formulas meeting the 2.0 [mu]g/100 kcal requirement. However, selenium 
deficiency is extremely rare, occurring primarily in areas of the world 
where the levels of selenium in the environment are low, such as China 
(Ref. 1). Therefore, it is not possible to quantify benefits accrued as 
a result of this rule and benefits will be discussed qualitatively.
    The consequences of selenium deficiency may be of greatest concern 
in infants and children, who have relatively greater requirements for 
selenium than adults due to their rapid growth (Ref. 1). According to 
Daniels, et al. (2008), suboptimal selenium status is associated with a 
range of negative health outcomes including thyroid and immune 
dysfunction, viral infection, cardiovascular disease, inflammatory 
conditions, infertility, and an increased risk of some cancers (Ref. 
5). Overt selenium deficiency is manifested as Keshan disease, an 
endemic fatal cardiomyopathy. Because infant formula may be an infant's 
only source of nutrition, the potential for developing a deficiency is 
averted if selenium is added to the formula.

XIII. Summary of Costs and Benefits of This Proposed Rule

    The total costs of this proposed rule, if finalized, consist of one 
time reformulation costs, one time submission costs and one time 
relabeling costs. The total cost ranges between about $4 million and 
$28 million. Because the costs of this proposed rule are one time only 
costs, no annual costs are estimated for this proposal. Furthermore, 
because selenium deficiency is so rare, it is not possible to quantify 
benefits from any final rule resulting from this proposal.
    Option 3: Finalize the proposed rule and make the provisions 
effective 12 months after publication.
    In this option, firms are required to meet the requirements of the 
proposed rule for infant formula, that is, have formulas contain 
selenium at 2.0 [mu]g and not more than 7.0 [mu]g for each 100 
kilocalories of the infant formula, and have manufacturers add selenium 
to the list of nutrients on infant formula labels. However, under 
Option 3, industry would have at least 12 months before they were 
required to comply with the rule.

XIV. Costs of Option 3

    For this option, the primary costs of this proposed rule will be 
reformulation costs resulting from the firm that needs to add slightly 
more selenium to certain infant formulas in order to comply with any 
final rule resulting from this proposal, along with relabeling and 
submission costs. These costs are presented in 2012 dollars. In 
contrast to Option 2, relabeling costs for this option are less, 
because of the estimation of the cost model that, over a longer period 
of time, any labeling change is more likely to be able to be 
coordinated with a change in a label that may already be scheduled, and 
will diminish the need to, for example, purchase and apply stickers to 
packages affected by the change. As in Option 2, the Agency 
acknowledges the uncertainty in this estimation and how it may 
specifically apply to the infant formula industry and requests comment 
regarding the extent to which the effective date is likely to affect 
the cost of compliance with this proposed rule.

                                      Table 4--Summary of Costs of Option 3
----------------------------------------------------------------------------------------------------------------
                                                                        Low           Medium           High
----------------------------------------------------------------------------------------------------------------
Reformulation Cost..............................................        $491,188      $2,112,136      $4,257,760
One Time Submission Cost........................................             529             529             529
Relabeling Costs................................................         438,747         765,439       1,271,285
                                                                 -----------------------------------------------
    Total Cost of Option 3......................................         930,464       2,878,104       5,529,574
----------------------------------------------------------------------------------------------------------------

Therefore, the costs from this rule, as shown in table 4, range from 
about $930,464 to about $5.5 million.

XV. Benefits of Option 3

    Benefits from this option are identical to Option 2, however, under 
this option, benefits are delayed by 6 months. The potential benefits 
from this proposed option are any cases of selenium deficiency avoided 
as a result of infant formulas meeting the 2.0 ug/100kcal requirement. 
As stated earlier, selenium deficiency is extremely rare, occurring 
primarily in areas of the world where the levels of selenium in the 
environment are low (Ref. 1).

XVI. Preliminary Regulatory Flexibility Analysis

    FDA has examined the economic implications of this proposed rule as 
required by the Regulatory Flexibility Act (5 U.S.C. 601-612). If a 
rule has a significant economic impact on a substantial number of small 
entities, the Regulatory Flexibility Act requires Agencies to analyze 
regulatory options that would lessen the economic effect of the rule on 
small entities. FDA finds that, under the Regulatory Flexibility Act (5 
U.S.C. 605(b)), this proposal, if finalized, will not have a 
significant impact on a substantial number of small entities, as only 
one firm is affected by this rule and it is considered large by Small 
Business Administration standards.

[[Page 22449]]

XVII. Paperwork Reduction Act of 1995

    This proposed rule contains information collection provisions that 
are subject to review by the Office of Management and Budget (OMB) 
under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). A 
description of these provisions is given in this section of the 
document with an estimate of the annual third-party disclosure burden. 
Included in the burden 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 the following topics: (1) Whether the 
proposed 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 proposed 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: Third-Party Disclosure Requirements for Selenium in Infant 
Formula
    Description of Respondents: The respondents to this information 
collection are manufacturers of infant formula marketed in the United 
States.
    Description: The proposed rule, if finalized, would revise Sec.  
107.10(a) to require that selenium be listed in the nutrient list on 
the label for all infant formulas. In particular, in the nutrient list, 
selenium would be required to be listed between iodine and sodium and 
the amount per 100 calories declared; and, because selenium would be a 
required ingredient in infant formula, selenium would also be required 
to be declared in the formula's ingredient statement by its common or 
usual name and positioned according to the descending order of its 
predominance in the formula, under Sec.  101.4. The present version of 
Sec.  107.10(a) is approved by OMB in accordance with the PRA and has 
been assigned OMB control number 0910-0256. This proposed rule, if 
finalized, would modify the information collection associated with the 
present version of Sec.  107.10(a) by adding 23 hours to the burden 
associated with the collection. A manufacturer not in compliance with 
the new minimum and maximum levels for selenium in infant formula would 
be required to make a one-time change to the nutrient list information 
disclosed to consumers on the label of its infant formula, to account 
for the required change in the amount of selenium in its products. The 
nutrient information disclosed by manufacturers on the infant formula 
label is necessary to inform purchasers of the value of the infant 
formula. As discussed previously in this document, FDA has the 
authority to revise the statement of the amounts of nutrients required 
for infant formula labeling in Sec.  107.10(a)(2).
    FDA estimates the burden of this collection of information as 
follows:

                                               Table 5--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                           Number of
            21 CFR section                Number of     disclosures per    Total annual        Average burden per         Total hours     Total capital
                                         respondents       respondent      disclosures             disclosure                                  cost
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sec.   107.10 Nutrient labeling for                 1               46               46   0.5 (30 minutes)............              23         $765,439
 infant formula.
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no operating and maintenance costs associated with this collection of information.

    FDA tentatively concludes that the additional burden to disclose 
selenium in the ingredient statement resulting from the proposed 
amendment of Sec.  107.10 would be negligible because all U.S. infant 
formula manufacturers currently add selenium as an ingredient to their 
infant formula products, and all manufacturers currently disclose the 
selenium in the ingredient statement, as specified by Sec.  101.4. 
Additionally, all manufacturers currently disclose selenium in the 
nutrient list, as required by Sec.  107.10(b)(5). Only one manufacturer 
produces infant formula that would not meet the requirements of this 
rule, if finalized, and would thus need to be reformulated. Under 
proposed Sec.  107.10(a)(2), this one manufacturer would need to make a 
one-time labeling change to modify its nutrient list to account for the 
addition of more selenium to its infant formula.
    The third-party disclosure burden consists of the setup time 
required to design a revised label and incorporate it into the 
manufacturing process. Based upon its knowledge of food and dietary 
supplement labeling, FDA estimates that the affected manufacturer would 
require less than 0.5 hour per product to modify the label's nutrient 
list to reflect the addition of more selenium to the product. The 
Regulatory Impact Analysis estimates that this manufacturer produces 46 
separate infant formulas that would need to be reformulated, and thus 
require relabeling. The one-time third-party disclosure burden for the 
proposed rule is estimated in table 5 of this document.
    The final column of table 5 gives the estimated capital cost 
associated with relabeling. This is the cost of designing a revised 
label and incorporating it into the manufacturing process. The cost 
stated in table 5, $765,439, is based on the estimate in the Regulatory 
Impact Analysis under Option 3, which assumes that the proposed rule is 
finalized with an effective date of 1 year after publication. These 
costs are based on the estimation of the cost model that, over a longer 
period of time, any labeling change is more likely to be able to be 
coordinated with a change in a label that may already be scheduled, and 
will diminish the need to, for example, purchase and apply stickers to 
packages affected by the change. Additionally, because of the change in 
formulation of its products that would be required if the rule is 
finalized as proposed, a manufacturer would need to determine whether 
they are required to make a one-time submission to FDA before the first 
processing of its formulas, as required by section 412(d)(3) of the 
FD&C Act. This reporting requirement is approved by OMB under OMB 
control number 0910-0256. The current hour burden approved by OMB for 
section 412(d) of the FD&C Act is 10 hours per report. Based on the 
Agency's experience with infant formula submissions, FDA estimates that 
the affected manufacturer will submit one report that will cover all 46 
reformulated infant formulas. In a future request for extension of the 
0910-0256 information collection, FDA will include the additional 
report in its estimates.

[[Page 22450]]

    To ensure that comments on 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, 
or emailed to oira_submission@omb.eop.gov. All comments should be 
identified with the title ``Third-Party Disclosure Requirements for 
Selenium in Infant Formula.''
    In compliance with the Paperwork Reduction Act of 1995 (44 U.S.C. 
3407(d)), the Agency has submitted the information collection 
provisions of this proposed rule to OMB for review. Interested persons 
are requested to send comments regarding information collection by May 
16, 2013, to the Office of Information and Regulatory Affairs, OMB.

XVIII. How do you submit comments on this rule?

    Interested persons may submit either electronic comments regarding 
this document to http://www.regulations.gov or written comments to the 
Division of Dockets Management (see ADDRESSES). It is only necessary to 
send one set of comments. Identify comments 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, and will be posted to the docket at http://www.regulations.gov.

XIX. References

    The following references have been placed on display in the Dockets 
Management Branch (see ADDRESSES) and may be seen by interested persons 
between 9 a.m. and 4 p.m., Monday through Friday.

1. Food and Nutrition Board. Institute of Medicine. Dietary 
Reference Intakes for Vitamin C, Vitamin E, Selenium, and 
Carotenoids. Washington, DC: National Academy Press, p. 21-33; 292-
299; 315-316, 2000.
2. Food and Nutrition Board. National Research Council. Recommended 
Dietary Allowances. 10th Edition. Washington, DC: National Academy 
Press, p. 221, 1989.
3. Raiten, D. J., J. M. Talbot, and J. H. Waters, ``Assessment of 
Nutrient Requirements for Infant Formulas,'' Journal of Nutrition, 
128: 2059S-2249S, 1998.
4. Koletzko, B., S. Baker, G. Cleghorn, U. F. Neto, et al., ``Global 
Standard for the Composition of Infant Formula. Recommendations of 
an ESPGHAN Coordinated International Expert Group,'' Journal of 
Pediatric Gastroenterology and Nutrition, 41:584-599, 2005.
5. Daniels, L., R.A. Gibson, K. Simmer, P. Van Dael, M. Makrides, 
``Selenium Status of Term Infants Fed Selenium-Supplemented Formula 
in a Randomized Dose-Response Trial,'' American Journal of Clinical 
Nutrition, 88:70-76, 2008.
6. Centers for Disease Control and Prevention (CDC). National Center 
for Health Statistics (NCHS). National Health and Nutrition 
Examination Survey Data. Hyattsville, MD: U.S. Department of Health 
and Human Services, Centers for Disease Control and Prevention, 
2013.
7. Codex Alimentarius Commission, ``Standards for Infant Formulas 
for Special Medical Purposes Intended for Infants, 72-1981,'' 1981.

List of Subjects in 21 CFR Part 107

    Exempt infant formulas, Food labeling, General provisions, Infant 
formula, Infant formula recalls, Infants and children, Labeling, 
Nutrition, Nutrient requirements, Reporting and recordkeeping 
requirements, Signs and symbols.

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

PART 107--INFANT FORMULA

    The authority citation for 21 CFR part 107 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 343, 350a, 371.

0
1. In Sec.  107.10, revise paragraph (a)(2) to read as follows:

Sec.  107.10  Nutrient Information.

    (a) * * *
    (2) A statement of the amount of each of the following nutrients 
supplied by 100 kilocalories:

------------------------------------------------------------------------
               Nutrients                      Unit of  measurement
------------------------------------------------------------------------
Protein...............................  Grams.
Fat...................................  Do.
Carbohydrate..........................  Do.
Water.................................  Do.
Linoleic acid.........................  Milligrams.
Vitamins:
  Vitamin A...........................  International Units.
  Vitamin D...........................  Do.
  Vitamin E...........................  Do.
  Vitamin K...........................  Micrograms.
  Thiamine (Vitamin B1)...............  Do.
  Riboflavin (Vitamin B2).............  Do.
  Vitamin B6..........................  Do.
  Vitamin B12.........................  Do.
  Niacin..............................  Do.
  Folic acid (Folacin)................  Do.
  Pantothenic acid....................  Do.
  Biotin..............................  Do.
  Vitamin C (Ascorbic acid)...........  Milligrams.
  Choline.............................  Do.
  Inositol............................  Do.
Minerals:
  Calcium.............................  Milligrams.
  Phosphorus..........................  Do.
  Magnesium...........................  Do.
  Iron................................  Do.
  Zinc................................  Do
  Manganese...........................  Micrograms.
  Copper..............................  Do.
  Iodine..............................  Do.
  Selenium............................  Do.
  Sodium..............................  Milligrams.
  Potassium...........................  Do.
  Chloride............................  Do.
------------------------------------------------------------------------

* * * * *
0
2. In Sec.  107.100, revise paragraph (a) to read as follows:

Sec.  107.100  Nutrient specifications.

    (a) An infant formula shall contain the following nutrients at a 
level not less than the minimum specified and not more than the maximum 
level specified for each 100 kilocalories of the infant formula in the 
form prepared for consumption as directed on the container:

----------------------------------------------------------------------------------------------------------------
                  Nutrients                           Unit of measurement         Minimum level   Maximum level
----------------------------------------------------------------------------------------------------------------
Protein......................................  Grams...........................            1.8               4.5
Fat..........................................  do..............................            3.3               6.0
                                               Percent calories................           30                54
Linoleic acid................................  Milligrams......................          300     ...............
                                               Percent calories................            2.7   ...............
----------------------------------------------------------------------------------------------------------------
                                                    Vitamins
----------------------------------------------------------------------------------------------------------------
Vitamin A....................................  International Units.............          250               750
Vitamin D....................................  do..............................           40               100
Vitamin E....................................  do..............................            0.7   ...............

[[Page 22451]]

 
Vitamin K....................................  Micrograms......................            4     ...............
Thiamine (Vitamin B1)........................  do..............................           40     ...............
Riboflavin (Vitamin B2)......................  do..............................           60     ...............
Vitamin B6...................................  do..............................           35     ...............
Vitamin B12..................................  do..............................            0.15  ...............
Niacin \1\...................................  do..............................          250     ...............
Folic Acid (folacin).........................  do..............................            4     ...............
Pantothenic acid.............................  do..............................          300     ...............
Biotin \2\...................................  do..............................            1.5   ...............
Vitamin C (ascorbic acid)....................  Milligrams......................            8     ...............
Choline \2\..................................  do..............................            7     ...............
Inositol \2\.................................  do..............................            4     ...............
----------------------------------------------------------------------------------------------------------------
                                                    Minerals
----------------------------------------------------------------------------------------------------------------
Calcium......................................  do..............................           60     ...............
Phosphorus...................................  do..............................           30     ...............
Magnesium....................................  do..............................            6     ...............
Iron.........................................  do..............................            0.15              3.0
Zinc.........................................  do..............................            0.5   ...............
Manganese....................................  Micrograms......................            5     ...............
Copper.......................................  do..............................           60     ...............
Iodine.......................................  do..............................            5                75
Selenium.....................................  do..............................            2                 7
Sodium.......................................  Milligrams......................           20                60
Potassium....................................  do..............................           80               200
Chloride.....................................  do..............................           55               150
----------------------------------------------------------------------------------------------------------------
 \1\ The generic term ``niacin'' includes niacin (nicotinic acid) and niacinamide (nicotinamide).
 \2\ Required only for non-milk-based infant formulas.

* * * * *

    Dated: April 10, 2013.
Leslie Kux,
Assistant Commissioner for Policy.
[FR Doc. 2013-08855 Filed 4-15-13; 8:45 am]
BILLING CODE 4160-01-P