[Federal Register Volume 80, Number 120 (Tuesday, June 23, 2015)]
[Rules and Regulations]
[Pages 35834-35841]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 2015-15394]


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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, HHS.

ACTION: Final rule.

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SUMMARY: The Food and Drug Administration (FDA or we) is amending 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: This final rule is effective June 22, 2016. See section VII of 
this document for information on the filing of objections. Submit 
either electronic or written objections and requests for a hearing by 
July 23, 2015.

ADDRESSES: You may submit either electronic or written objections and/
or requests for a hearing, identified by Docket No. FDA-2013-N-0067, by 
any of the following methods:

Electronic Submissions

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

Written Submissions

    Submit written objections in the following ways:
     Mail/Hand delivery/Courier (for paper 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 Docket No. 
FDA-2013-N-0067 for this rulemaking. All objections received may be 
posted

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without change to http://www.regulations.gov, including any personal 
information provided. For additional information on submitting 
objections, see the ``Objections'' heading of the SUPPLEMENTARY 
INFORMATION section of this document.
    Docket: For access to the docket to read background documents, 
comments, or objections 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 and/or go to 
the Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, 
Rockville, MD 20852.

FOR FURTHER INFORMATION CONTACT: Leila Beker, Center for Food Safety 
and Applied Nutrition (HFS-850), Food and Drug Administration, 5100 
Paint Branch Pkwy., College Park, MD 20740, 240-402-1451.

SUPPLEMENTARY INFORMATION: 

I. What is the background and legal authority of this final rule?

A. Background

    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. This 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 in FDA regulations at Sec.  
107.100(a) (21 CFR 107.100(a)), specifies that infant formulas must 
contain 29 nutrients; minimum levels for each nutrient and maximum 
levels for 9 of the nutrients are also specified. In 1989, the Food and 
Nutrition Board of the National Research Council established a 
Recommended Dietary Allowance 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. 1).
    In the Federal Register of April 16, 2013 (78 FR 22442), we 
proposed to amend the nutrient specifications for infant formula to 
include selenium as a required nutrient in Sec.  107.100(a). We also 
proposed to establish minimum and maximum levels for selenium in infant 
formulas because evidence exists for both deficiency and toxicity of 
selenium. We proposed 2.0 [mu]g selenium per 100 kilocalories (/100 
kcal) as the minimum level of selenium in infant formulas and 7.0 
[mu]g/100 kcal as the maximum level of selenium in infant formulas.
    Scientific evidence from multiple sources supported the proposed 
levels. Specifically, for the proposed requirements, we considered 
scientific evidence in: (1) The Institute of Medicine's (IOM) ``Dietary 
Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids'' 
(Ref. 2); (2) the Life Sciences Research Office's ``Assessment of 
Nutrient Requirements for Infant Formulas'' by Raiten et al. (Ref. 3); 
(3) ``Global Standard for the Composition of Infant Formula. 
Recommendations of an ESPGHAN [European Society for Paediatric 
Gastroenterology, Hepatology and Nutrition] Coordinated International 
Expert Group'' by Koletzko et al. (Ref. 4); and (4) ``Selenium Status 
of Term Infants Fed Selenium-Supplemented Formula in a Randomized Dose-
Response Trial'' by Daniels et al. (Ref. 5). We also searched the 
scientific literature from 1998 through 2012 for published studies not 
included in these reports.
    In addition, we proposed to amend the labeling requirements for 
infant formula in Sec.  107.10(a)(2) to add selenium to the list of 
nutrients along with the requirement to list the amount of selenium per 
100 kcal in the formula.

B. Legal Authority

    Section 412(i) of the FD&C Act contains a table of nutrients 
(including minimum and, in some cases, maximum levels for 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. Our 
regulations establishing the table of nutrients are codified at Sec.  
107.100.
    The final rule amends Sec.  107.100 to add selenium to the list of 
nutrients required for infant formula. The legal authority for the 
amendment to Sec.  107.100 comes from section 412(i)(2) of the FD&C 
Act.
    The final rule also requires adding selenium to the statement of 
the amounts of nutrients required for infant formula labeling in Sec.  
107.10(a)(2). ``Infant formula'' is defined as a food for ``special 
dietary use'' under section 201(z) of the FD&C Act (21 U.S.C. 321(z)). 
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 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.

II. What issues did the comments raise? What are FDA's responses to the 
comments?

    We invited public comment on the proposed rule. The comment period 
closed on July 1, 2013. We received fewer than 20 comments. Overall, 
the comments supported the addition of selenium to infant formula and 
agreed that selenium is an essential nutrient. We summarize and respond 
to the comments on the proposed rule and describe the final rule in 
this section. For ease of reading, we preface each comment discussion 
with a numbered ``Comment,'' and each response by a corresponding 
numbered ``Response.'' We have numbered each comment to help 
distinguish among different topics. The number assigned is for 
organizational purposes only and does not signify the comment's value, 
importance, or the order in which it was received.

A. The Addition of Selenium to the Statement of the Amounts of 
Nutrients (Sec.  107.10(a)(2))

    The proposed rule would amend the infant formula nutrient labeling 
and nutrient specification regulations at Sec. Sec.  107.10 and 
107.100, respectively. Proposed Sec.  107.10(a)(2) would add selenium 
to the statement of the amounts of nutrients required for infant 
formula labeling.
    We did not receive any comments on proposed Sec.  107.10(a)(2). 
However, we note that we have revised Sec.  107.10(a)(2) in this final 
rule to correspond to changes resulting from an interim final rule that 
appeared in the Federal Register on February 10, 2014 (79 FR 7934), and 
later affirmed in a final rule that appeared in the Federal Register on 
June 10, 2014 (79 FR 33057). In brief, Sec.  107.10(a)(2) was reworded 
by replacing ``A statement of the amount of each of the following 
nutrients supplied by 100 kilocalories'' with ``A statement of the 
amount, supplied by 100 kilocalories, of each of the following 
nutrients and of any other nutrient added by the manufacturer.''

B. Minimum and Maximum Levels of Selenium (Sec.  107.100)

    Proposed Sec.  107.100(a) would add selenium to the list of 
required nutrients in infant formula. The proposal also

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would 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. We proposed to set 
2.0 [mu]g selenium/100 kcal as the minimum level of selenium in infant 
formulas and 7.0 [mu]g/100 kcal as the maximum level of selenium in 
infant formulas. Since the publication of the proposed rule, we have 
conducted a search of the scientific literature to identify whether 
additional studies on selenium requirements of infants were published 
after we issued our proposal. We did not find any relevant studies in 
our search.
    (Comment 1) One comment suggested we decrease the minimum level of 
selenium to 1.6 [mu]g/100 kcal. The comment pointed to analytical 
variability that can occur between laboratories when testing the levels 
of selenium. According to the comment, due to this analytical 
variability, a minimum selenium level of 1.6 [mu]g/100 kcal will likely 
result in manufacturers' formulating to deliver selenium levels close 
to 2.0 [mu]g/100 kcal to ensure products do not fall below the minimum.
    (Response 1) We decline to lower the minimum level of selenium in 
infant formula to 1.6 [mu]g/100 kcal to accommodate analytical 
variability that can occur between laboratories as the comment 
suggested. The level of any substance (including nutrients, food 
additives, or contaminants) established for regulatory purposes must be 
a value that is based on and true to the available scientific evidence. 
We recognize that analytical variability is always present and manage 
this matter under our compliance program. We also note that lowering 
the minimum level of selenium would not change the analytical 
variability, and the tested level of selenium might fall below whatever 
minimum level is set, due to analytical variability. For example, if 
the minimum level was lowered to 1.6 [mu]g/100 kcal, the tested level 
of selenium might fall below 1.6 [mu]g/100 kcal due to analytical 
variability. However, on our own initiative we have revised proposed 
Sec.  107.100(a) to insert the word ``level'' between the words 
``minimum'' and ``specified'' in light of an inadvertent omission in 
the proposed rule.
    (Comment 2) One comment said that the minimum level of selenium 
should be in the range reported in breast milk and specifically 
recommended the level of 1.6 [mu]g selenium/100 kcal, consistent with 
the mean concentration of selenium in breast milk reported by Daniels 
et al. (2008). The comment continued, saying it was not aware of any 
reports of selenium deficiency in breast-fed infants or at this 
concentration of selenium in infant formula. The comment also stated 
that we did not consider the data from the breast-fed control group in 
the Daniels et al. study.
    (Response 2) With regard to this comment suggesting that the 
selenium concentration in human milk (and more specifically, the level 
of 1.6 [mu]g/100 kcal reported in the Daniels et al. study) be used as 
the basis for the required minimum selenium level in infant formula, 
the scientific evidence we discussed in the proposed rule (78 FR 22442 
at 22444) was more broadly based. The discussion in the proposed rule 
considered the levels of selenium in human milk from the studies used 
to establish the adequate intake (AI) for selenium by the IOM and the 
levels of selenium in infant formulas fed in the randomized and double-
blinded dose-response study in infants by Daniels et al. (2008).
    Specifically, as discussed in the proposed rule (78 FR 22442 at 
22444), the IOM established an AI for selenium of 15.0 [mu]g/day 
(approximately 2.1 [mu]g/kg body weight/day) for infants 0 to 6 months 
of age based on the average concentration of selenium in human milk 
from healthy women from 2 to 6 months of lactation as reported in four 
studies. The study by Daniels et al. was published after the IOM 
established the AI for selenium for infants 0 to 6 months of age, and 
the concentration of selenium in human milk reported in that study was 
not among the studies considered in the establishment of the AI. We 
note that the mean concentration of selenium in human milk in the 
studies included by the IOM in setting the AI for infants 0 to 6 months 
of age was 18 [mu]g/L and that reported by Daniels et al. was 10.7 
[mu]g/L.
    The study by Daniels et al. provides direct evidence of the effect 
of selenium concentration of infant formula on the circulating 
biochemical indicators of selenium status in infants. As described in 
the proposed rule (78 FR 22442 at 22444), this study included a control 
formula that contained 0.9 [mu]g selenium/100 kcal (considered by the 
investigators to be a low-selenium formula) and two test formulas that 
contained 1.9 [mu]g selenium/100 kcal or 3.1 [mu]g selenium/100 kcal. 
The level of selenium in the formula containing 1.9 [mu]g/100 kcal was 
somewhat higher than the level in human milk reported in the Daniels et 
al. study and close to the AI set by the IOM. In our consideration of 
the study by Daniels et al., we regarded the data from the human milk-
fed infants as reference data, with the direct comparators being the 
indicators of selenium status of infants fed the formulas containing 
the three levels of selenium. The plasma and erythrocyte indicators of 
selenium status for both test formulas did not differ from each other 
but differed with statistical significance from the control formula. 
Compared to the infants fed the formula containing 1.9 [mu]g selenium/
100 kcal, infants fed the formula containing 3.1 [mu]g selenium/100 
kcal excreted more selenium in the urine. This increase in urinary 
selenium was found to be statistically significant. Combined with the 
finding of no dose-related changes in the circulating indicators of 
selenium status in infants fed formulas containing 1.9 [mu]g selenium/
100 kcal or 3.1 [mu]g selenium/100 kcal, this dose-related increase in 
urinary selenium 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. Much of the selenium intake above the 
level of 1.9 [mu]g selenium/100 kcal was apparently eliminated from the 
body through the body's homeostatic mechanisms.
    As effects on indicators of selenium status have not been evaluated 
in infants fed formulas with concentrations of selenium between 0.9 
[mu]g selenium/100 kcal and 1.9 [mu]g selenium/100 kcal, there are no 
data to support lowering the minimum level of selenium in infant 
formula from 2.0 [mu]g/100 kcal to 1.6 [mu]g/100 kcal. The scientific 
evidence discussed previously and in section III.A. of the proposed 
rule (78 FR 22442 at 22443) continues to justify 2.0 [mu]g selenium/100 
kcal as the minimum level for selenium in infant formulas.
    (Comment 3) In support of a lower minimum level for selenium in 
infant formula, one comment pointed out that the Codex Alimentarius 
infant formula standard and the European Union Directive on Infant 
Formulae and Follow-On Formulae recommend a minimum level of selenium 
in infant formula of 1.0 [mu]g selenium/100 kcal.
    (Response 3) The level of 1.0 [mu]g/100 kcal as the minimum level 
for selenium in infant formula was adopted by the Codex Alimentarius in 
2007 for its Standard for Infant Formula and Formulas for Special 
Medical Purposes Intended for Infants (Codex Stan 72-1981) (Ref. 6) 
based on recommendation of this level by an International Expert Group 
(IEG) of the ESPGHAN (Ref. 4). The IEG recommended 1.0 [mu]g selenium/
100 kcal for infant formula based on the median selenium content of 
human milk and an established history of apparent safe use. However, as

[[Page 35837]]

described in the proposed rule (78 FR 22442 at 22444), no information 
was provided regarding the details of how such information was used in 
making the recommendation for 1.0 [mu]g selenium/100 kcal in infant 
formula. In addition, the recommendation of the IEG was made in 2005 
before the dose-response study of Daniels et al. was published in 2008, 
and data from that study suggest that a level of 1.9 [mu]g selenium/100 
kcal in infant formula meets infants' selenium needs. Further, 
although, as noted in the comment, the level of 1.0 [mu]g/100 kcal was 
also adopted as the minimum level for selenium by the European Union in 
2006 for its Directive on Infant Formulae and Follow-On Formulae 
(Commission Directive 2006/141/EC), identification of a scientific 
basis for the selection of 1.0 [mu]g selenium/100 kcal was not included 
in the European Union Commission Directive.
    (Comment 4) One comment suggested raising the maximum level of 
selenium added to infant formula to 9.0 [mu]g/100 kcal. The comment 
said that the 9.0 [mu]g selenium/100 kcal would align the maximum level 
of selenium with the upper levels recommended in the Codex Alimentarius 
Standard for Infant Formula and Formulas for Special Medical Purposes 
Intended for Infants, and with the European Union Directive on Infant 
Formulae and Follow-on Formulae. The comment also stated that 9.0 [mu]g 
selenium/100 kcal is more aligned with the use of 8.0 [mu]g/100 kcal as 
the maximum value for selenium in the FDA Compliance Program Guidance 
Manual (CPGM).
    (Response 4) We decline to increase the maximum level of selenium 
in infant formula to 9.0 [mu]g selenium/100 kcal as the comment 
suggested. As noted in the response to comment 1 concerning the minimum 
level of selenium in infant formula, the maximum level of any substance 
(including nutrients, food additives, or contaminants) established for 
regulatory purposes must also be a value that is based on and true to 
the available scientific evidence.
    The level of 9.0 [mu]g selenium/100 kcal suggested in the comment 
is the maximum level recommended by the ESPGHAN IEG for infant formula. 
The report of the IEG stated that its recommendation was based on a 
history of safe use (not further described) and did not identify 
scientific data or other information relied upon for its recommendation 
for a maximum level of 9.0 [mu]g selenium/100 kcal that was 
subsequently adopted by Codex Alimentarius in 2007 for its Standard for 
Infant Formula and Formulas for Special Medical Purposes Intended for 
Infants (Codex Stan 72-1981). The level of 9.0 [mu]g selenium/100 kcal 
was also listed in the European Union Directive on Infant Formulae and 
Follow-on Formulae. We considered the level of 9.0 [mu]g selenium/100 
kcal; however, we could not determine the scientific basis for this 
level.
    Although we expressly invited comment regarding the proposed 
maximum level in infant formula 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 (78 FR 22442 at 
22445), we did not receive any comments that disagreed with the need 
for a maximum level or that provided a scientific basis that would 
support a change from the proposed level. The report of the IOM, which 
we relied upon to propose the maximum level of 7.0 [mu]g selenium/100 
kcal, identified the data (concentration of selenium in human milk not 
associated with known adverse effects) and the method of calculation 
used to estimate a Tolerable Upper Intake Level (UL) of 7.0 [mu]g/kg 
body weight/day for selenium intake of infants from 0 to 6 months of 
age. (As explained in the proposed rule (78 FR 22442 at 22444), a level 
of intake expressed as [mu]g/kg body weight/day is consistent with an 
infant formula concentration expressed in [mu]g/100 kcal.)
    With regard to the use of 8.0 [mu]g/100 kcal as a maximum in our 
CPGM, this level was incorporated into the CPGM when infant formula 
manufacturers in the United States began adding selenium to infant 
formulas starting as early as 1990 and preceded the establishment of 
the UL for infants 0 to 6 months of age by the IOM. We will update the 
minimum and maximum values for selenium in infant formula in our CPGM 
to align with the final rule.
    (Comment 5) One comment said that setting 7.0 [mu]g selenium/100 
kcal as the maximum level of selenium, which is the amount we proposed, 
would mean some manufacturers would need to reformulate their products 
that currently meet the 8.0 [mu]g selenium/100 kcal level that is 
listed in the FDA CPGM.
    (Response 5) Although the comment said that some manufacturers 
whose products currently meet the 8.0 [mu]g selenium/100 kcal level 
listed in the FDA CPGM would need to reformulate, it did not specify 
how many manufacturers or products would likely be affected or whether 
label changes would be required following any reformulations. It also 
did not provide estimates of possible costs resulting from establishing 
a maximum of 7.0 [mu]g selenium/100 kcal. Other comments indicated that 
any formula changes could be made in a cost effective and timely manner 
with an effective date 12 months after publication of the final rule 
(see comment 7).
    If some manufacturers who currently meet the 8.0 [mu]g selenium/100 
kcal level need to reformulate their products to avoid exceeding a 
selenium level of 7.0 [mu]g/100 kcal, such a reformulation would 
involve only a small reduction in the amount of selenium added to the 
formula. Manufacturers routinely make such small changes in the rates 
of addition of ingredients (which may or may not result in the need for 
label changes) as a fundamental part of their current good 
manufacturing practices and quality control programs to ensure the 
consistent production of infant formulas of high quality. These types 
of changes are generally not considered to be major changes and are 
reported to FDA in a ``before first processing'' submission by the 
manufacturers if the change may adulterate the product, as required by 
section 412(d)(3) of the FD&C Act and our regulations in 21 CFR 
106.140.

C. Allowance for Analytical Variability

    (Comment 6) One comment suggested that, in the absence of setting a 
higher maximum selenium level, FDA would need to establish a specific 
allowance for method bias to ensure that manufacturers can meet both 
the minimum and maximum selenium levels. The comment suggested an 
allowance of 30 percent to account for analytical variability.
    (Response 6) As noted in the response to comment 4, the maximum 
level of any substance must be a value that is based on and true to the 
available scientific evidence. For this reason, we are not setting a 
higher maximum value that would include an allowance for analytical 
variability or method bias. We are not aware of method bias (consistent 
over- or under-measurement of the actual concentration) in the analysis 
of selenium in infant formula. We acknowledge that analytical 
variability occurs between laboratories when testing the levels of 
nutrients in infant formula, and we manage this matter under our 
compliance program as necessary. Further, we decline to set a 30 
percent allowance for analytical variation for the chemical analysis of 
selenium in infant formula. The comment did not provide a reason for 
setting such a high allowance for analytical variation, and 30 percent 
variability is much higher than performance requirements for commonly 
used methods for chemical

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analysis of minerals in infant formula, which typically is about 10 to 
15 percent.

D. Effective Date

    In the Regulatory Impact Analysis of the proposed rule, we analyzed 
three options with respect to an effective date: (1) Take 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 (78 FR 22442 at 22446).
    (Comment 7) Two comments supported FDA's option 3 in the proposed 
rule to make the final rule effective 12 months after publication to 
allow for cost effective and timely changes with no anticipated impact 
on infant health. One comment explained that because there have been no 
reports of full-term, breast-fed infants in the United States with 
evidence of selenium deficiency, there would be no anticipated impact 
to infant health due to a 6-month delay in the rule's effective date 
(from 6 months in option 2 to 12 months in option 3 of the Regulatory 
Impact Analysis of the proposed rule).
    (Response 7) The final rule will be effective 12 months after 
publication of this document (see DATES). This will allow the industry 
to make any needed reformulations and label changes to their infant 
formula products in the 12-month period that the comment identified as 
cost effective and timely for needed changes.

E. Miscellaneous Comments

    Several comments addressed matters that were not specific to a 
particular provision in the proposed rule and/or that were not covered 
by the rule. We summarize and address those comments here.
    (Comment 8) One comment suggested that FDA recommend or encourage 
the use of the organic form of selenium, selenomethionine, rather than 
the inorganic forms, sodium selenite or sodium selenate. The comment 
explained that selenomethionine is the selenium compound incorporated 
into body proteins and is available in dietary supplements or from 
brewer's yeast.
    (Response 8) FDA's specifications for infant formula composition in 
Sec.  107.100 identify nutrients that must be included in the formula. 
The regulations do not specify ingredients that can serve as sources of 
the nutrients, except for vitamin K in Sec.  107.100(c). We decline to 
specify the form of selenium in infant formula because we do not have 
information that indicates that any specific source of selenium should 
be used in infant formula. Our recently published current good 
manufacturing practices for infant formulas require that ingredients 
used in infant formulas be safe and suitable for use in infant formula. 
Specifically, under Sec.  106.40(a), the only substances that may be 
used in an infant formula are substances that are safe and suitable for 
use in infant formula under the applicable food safety provisions of 
the FD&C Act; that is, a substance is used in accordance with the 
Agency's food additive regulations, is generally recognized as safe for 
such use, or is authorized by a prior sanction.
    (Comment 9) One comment agreed with the proposed selenium levels 
``unless a pediatrician otherwise recommends an alternative dosage 
because of a peculiar deficiency of selenium.'' The comment did not 
explain the circumstances under which a pediatrician would recommend an 
``alternative dosage.''
    (Response 9) The final rule adds selenium to the list of required 
nutrients in infant formula and establishes minimum and maximum levels 
of selenium in infant formula. Manufacturers will be required to add 
selenium to infant formula within the established bounds as of the 
effective date of this rule. The rule does not apply to what physicians 
may do within the practice of medicine. Thus, matters pertaining to the 
practice of pediatric medicine are outside the scope of this 
rulemaking.
    (Comment 10) Another comment suggested that FDA consider 
establishing a higher maximum for vitamin D based on recent American 
Academy of Pediatrics and IOM recommendations.
    (Response 10) The final rule adds selenium to the list of required 
nutrients in infant formula and establishes minimum and maximum levels 
of selenium in infant formula. With respect to vitamin D and infant 
formula, we may, as resources permit, reevaluate all the minimum and 
maximum required nutrient levels for infant formula in separate 
rulemakings.
    (Comment 11) One comment supported the proposal to require the 
addition of selenium in infant formula. The comment stated that a child 
that does not receive enough selenium in the diet is at risk of 
developing Keshan disease.
    (Response 11) FDA agrees that Keshan disease is linked to selenium 
deficiency. The preamble to the proposed rule discussed the known 
biological functions of selenium and Keshan disease (a cardiomyopathy 
that occurs almost exclusively in children) (see 78 FR 22442 at 22443).

III. What is the environmental impact of this final 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.

IV. Federalism

    FDA has analyzed this final rule in accordance with the principles 
set forth in Executive Order 13132. We have determined that the rule 
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 have concluded that the 
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.

V. Executive Order 12866 and Executive Order 13563: Cost Benefit 
Analysis

    On April 16, 2013, we proposed to amend our 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 (78 FR 22442). The 
Economic Impact Analysis in the proposed rule explained the economic 
impact of the changes to regulations at part 107. We did not receive 
any comments on the economic analysis of the proposed rule.
    FDA has examined the impacts of this final 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). FDA has developed a regulatory impact analysis that presents 
the benefits and costs of this proposed rule (Ref. 7). We believe that 
the final rule will not be a

[[Page 35839]]

significant regulatory action as defined by Executive Order 12866.

VI. Paperwork Reduction Act of 1995

    This final 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 (PRA) (44 U.S.C. 3501-3520). The 
title, description, and respondent description of the information 
collection provisions are shown in the following paragraphs with an 
estimate of the annual third-party disclosure burden. Included in the 
estimate is the time for reviewing instructions, searching existing 
data sources, gathering and maintaining the data needed, and completing 
and reviewing each collection of information.
    Title: 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 final rule revises Sec.  107.10(a)(2) to require 
that selenium be listed in the nutrient list on the label for all 
infant formulas. In particular, in the nutrient list, selenium must be 
listed between iodine and sodium and the amount per 100 calories 
declared; and because selenium is a required ingredient in infant 
formula, selenium is 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 (21 CFR 101.4). The present version of Sec.  
107.10(a)(2) is approved by OMB in accordance with the PRA and has been 
assigned OMB control number 0910-0256. This final rule modifies the 
information collection associated with the present version of Sec.  
107.10(a)(2) 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 1--Estimated Annual Third-Party Disclosure Burden \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                               Number of
              21 CFR section                   Number of      disclosures    Total annual        Average burden per         Total hours    Total capital
                                              respondents   per respondent    disclosures            disclosure                                cost
--------------------------------------------------------------------------------------------------------------------------------------------------------
Sec.   107.10(a)(2)--Nutrient labeling for               1              46              46  0.5 (30 minutes)                          23        $792,439
 infant formula.
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ There are no operating and maintenance costs associated with this collection of information.

    FDA concludes that there will be no additional burden associated 
with the requirement to disclose selenium in the ingredient statement 
as required under Sec.  101.4 because all infant formula manufacturers 
currently add selenium as an ingredient to their infant formula 
products that are sold in the United States, and all manufacturers 
currently disclose 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). Under 
Sec.  107.10(a)(2), only one manufacturer would need to make a one-time 
labeling change to modify the amount of selenium shown in the nutrient 
list on the labels of 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 our knowledge of food and dietary 
supplement labeling, we estimate 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. We 
estimate that this manufacturer produces 46 separate infant formulas 
that would require relabeling. The one-time third-party disclosure 
burden is estimated in table 1 of this document.
    The final column of table 1 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 1, $792,439, is estimated based on an effective date of 
1 year after publication. These costs are based on the cost model 
estimate that, over a longer period of time, any labeling change is 
more likely 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 information collection provisions in this final rule have been 
submitted to OMB for review as required by section 3507(d) of the PRA. 
The requirements were approved and assigned OMB control number 0910-
0256. This approval expires on 04/30/2018.
    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.

VII. Objections

    This rule is effective as shown in the DATES section, except as to 
any provisions that may be stayed by the filing of proper objections. 
If you will be adversely affected by one or more provisions of this 
regulation, you may file with the Division of Dockets Management (see 
ADDRESSES) either electronic or written objections. You must number 
each objection separately, and, within each numbered objection, you 
must specify with particularity the provision(s) to which you object, 
and the grounds for your objection. Within each numbered objection, you 
must specifically state whether you are requesting a hearing on the 
particular provision that you specify in that numbered objection. If 
you do not request a hearing for any particular objection, we will 
consider the absence of such a request as waiving the right to a 
hearing on that objection. If you request a hearing, your objection 
should include a detailed description and analysis of the specific 
factual information you intend to present in support of the objection 
in the event that a hearing is held.
    It is only necessary to send one set of documents. Identify 
documents with the

[[Page 35840]]

docket number found in brackets in the heading of this document. Any 
objections received in response to the regulation 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. We will publish notice of the objections that we 
have received or lack thereof in the Federal Register.

VIII. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at http://www.regulations.gov.

    1. Food and Nutrition Board, National Research Council, 
``Recommended Dietary Allowances,'' 10th ed., Washington, DC: The 
National Academies Press, p. 221, 1989.
    2. Food and Nutrition Board, Institute of Medicine, ``Dietary 
Reference Intakes for Vitamin C, Vitamin E, Selenium, and 
Carotenoids,'' Washington, DC: The National Academies Press, pp. 21-
33; 292-299; 315-316, 2000.
    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, and 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. Codex Alimentarius Commission, ``Standard for Infant Formula 
and Formulas for Special Medical Purposes Intended for Infants, 
Codex Stan 72-1981,'' 1981. Revised 2007.
    7. FDA/Center for Food Safety and Applied Nutrition, ``Infant 
Formula: The Addition of Minimum and Maximum Levels of Selenium to 
Infant Formula and Related Labeling Requirements, Final Regulatory 
Impact Analysis and Regulatory Flexibility Analysis,'' 2015. 
Available at: http://www.fda.gov/AboutFDA/ReportsManualsForms/Reports/EconomicAnalyses/.

List of Subjects in 21 CFR Part 107

    Food labeling, Infants and children, Nutrition, Reporting and 
recordkeeping requirements, Signs and symbols.
    For the reasons discussed in the preamble, under the Federal Food, 
Drug, and Cosmetic Act, and under authority delegated to the 
Commissioner of Food and Drugs, the Food and Drug Administration amends 
21 CFR part 107 as follows:

PART 107--INFANT FORMULA

0
1. The authority citation for 21 CFR part 107 continues to read as 
follows:


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


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


Sec.  107.10  Nutrient information.

    (a) * * *
    (2) A statement of the amount, supplied by 100 kilocalories, of 
each of the following nutrients and of any other nutrient added by the 
manufacturer:

 
------------------------------------------------------------------------
                 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.
------------------------------------------------------------------------


[[Page 35841]]

* * * * *

0
3. 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 level 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  ................
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: June 17, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-15394 Filed 6-22-15; 8:45 am]
 BILLING CODE 4164-01-P