requirements that relate to the adulteration provisions. FDA would
consider the submission under Sec.  106.120(c) of the interim final
rule to satisfy the verification submission requirement in Sec.
106.130 of the interim final rule for such formula. Therefore, FDA has
revised Sec.  106.130(a) in the interim final rule as follows: ``A
manufacturer shall, after the first production and before the
introduction into interstate commerce of a new infant formula (except
for a new infant formula that is for export only for which a submission
is received in compliance with Sec.  106.120(c)), verify in a written
submission to FDA at the address given in Sec.  106.110(a) that the
infant formula complies with the requirements of the Federal Food,
Drug, and Cosmetic Act and is not adulterated.''
2. Identification Number (Proposed Sec.  106.130(b)(1))
    (Comment 346) One comment suggested that proposed Sec.
106.130(b)(1), which would have required that the verification
submission include the identification number assigned by the Agency to
the new infant formula submission, should be qualified to state that
the verification submission must include this identification number, if
available. The comment asserted that oftentimes, the identification
number might not have been assigned or be available.
    (Response) FDA does not agree with this comment. Including the FDA-
assigned identification number in the verification submission is a
simple and reasonable means to permit FDA to link a verification
submission with the corresponding new infant formula submission. As
part of its standard procedures, FDA assigns an identification number
to each new infant formula submission received and includes this number
in a letter to the manufacturer acknowledging the new infant formula
submission. An infant formula manufacturer that does not receive, in a
timely way, an Agency acknowledgement letter in response to an infant
formula submission should contact FDA during the 90-day review period.
Accordingly, FDA is not revising proposed Sec.  106.130(b)(1), and this
provision is included in this interim final rule as proposed.
3. Verified Formula Matches Notified Formula (Proposed Sec.
106.130(b)(2))
    (Comment 347) One comment requested that proposed Sec.
106.130(b)(2), which would have required that the verification
submission include a statement that the infant formula to be introduced
into interstate commerce is the same as the infant formula that was the
subject of the new infant formula submission and for which the
manufacturer provided assurances in accordance with the requirements of
Sec.  106.120, should be modified to allow that if the infant formula
is not the same, the verification submission must include an
explanation of how the infant formula is different and why this
difference does not affect the quality factor requirements. In support
of this change, the comment stated that occasionally, a minor change
may be made to an infant formula between the time a 90-day submission
is made and the first production occurs and that, although these
changes are not expected to have an adverse impact on nutrient levels
or nutrient availability, the two formulations would not be ``the
same.'' Thus, the comment asserted that the verification submission
should provide a mechanism to record and explain these situations.
    (Response) FDA disagrees with this comment. Section 412(d)(2) of
the FD&C Act requires that an infant formula manufacturer submit a
written verification to FDA after the first production of an infant
formula (the ``first-produced'' formula) subject to section 412(c) of
the FD&C Act and before such formula is introduced into interstate
commerce. Therefore, the FD&C Act requires that the infant formula
addressed by the verification submission be the same formula that is
the subject of the new infant formula submission (the ``notified
formula'') previously submitted under section 412(c) of the FD&C Act.
In the proposed rule (61 FR 36154 at 36200), FDA tentatively concluded
that if a manufacturer can make the statement that would have been
required by proposed Sec.  106.130(b)(2), it means that the quality
factor assurances that the manufacturer provided in the new infant
formula submission continue to be relevant and applicable to the
product and thus, no additional information would need to be included
in the verification submission to demonstrate compliance with sections
412(b)(1) and 412(b)(2)(A) of the FD&C Act. FDA concludes that the
statement in proposed Sec.  106.130(b)(2) is necessary and is in lieu
of additional test results or records demonstrating compliance of the
``first-produced'' formula with these sections of the FD&C Act. If the
``first-produced'' formula differs from the ``notified formula'' in
ways that would constitute a major change or if the ``first-produced''
formula has otherwise been changed such that previous submission on
quality factor requirements and ingredient safety is no longer
relevant, the manufacturer could not truthfully make the statement in
proposed Sec.  106.130(b)(2). Thus, a manufacturer must evaluate
whether it can make the statement in Sec.  106.130(b)(2) in light of
any changes to the formula.
    For these reasons, FDA is not revising proposed Sec.  106.130(b)(2)
in response to this comment, and this provision is included in this
interim final rule as proposed.
4. Certification Statement (Proposed Sec.  106.130(b)(4))
    (Comment 348) One comment suggested that proposed Sec.
106.130(b)(4) be revised to delete the proposed requirement that a
verification submission contain a certification that the manufacturer
has established current good manufacturing practices, including quality
control procedures and in-process controls such as testing, designed to
prevent adulteration of this formula in accordance with subparts B and
C of part 106, and instead, to require that the verification submission
contain assurance that the manufacturer has done so. The comment states
that the suggested use of ``assurance'' was based on the provisions of
the Infant Formula Act relating to verification that refer specifically
to ``assurance'' as opposed to certification.
    (Response) FDA is not persuaded by this comment. First, although
FDA agrees that the word ``assurance'' is used in section 412 of the
FD&C Act, the comment does not describe the difference, material or
otherwise, between a suggested requirement that a manufacturer provide
``assurance'' and the proposed requirement that a manufacturer provide
a ``certification'' as to compliance with CGMP requirements. Absent
such a distinction, FDA sees no reason to change the language proposed.
The certification is the means by which a manufacturer provides the
assurance required under section 412(d) of the FD&C Act.
    Second, the proposed certification requirement is reasonable. FDA
is

responsible for reviewing the manufacturer's submission to ensure the
infant formula complies with the FD&C Act, and the Agency must be
satisfied that a manufacturer has, in accordance with subparts B and C
of part 106, established current good manufacturing practices,
including quality control procedures, in-process controls, and testing
required by CGMP that is designed to prevent adulteration of the
formula. Section 412(d)(2) of the FD&C Act requires that after the
first production of a new infant formula and before its introduction
into interstate commerce, the formula manufacturer submit written
verification summarizing test results and records demonstrating that
the formula complies with the requirements of section 412(b)(1),
(b)(2)(A), (b)(2)(B)(i), (b)(2)(B)(iii), (b)(3)(A), (b)(3)(C), and (i)
of the FD&C Act. As the Agency tentatively concluded in the proposed
rule, and concludes in this interim final rule, additional test results
or records demonstrating compliance with section 412(b)(2)(B)(i),
(b)(3)(A), and (b)(3)(C) of the FD&C Act are unnecessary because such
testing is subsumed under Sec.  106.130(b)(3) of the interim final rule
in the summary of test results for the level of each nutrient required
by Sec.  107.100. Section 106.130(b)(3) of the interim final rule
includes the test results for the level of nutrients required by 412(i)
of the FD&C Act. Further, the Agency concludes that it would be
unnecessary to require submission of the records demonstrating
compliance with section 412(b)(1) of the FD&C Act because the records
demonstrating compliance with quality factors would have been submitted
as part of the submission under section 412(c) and (d)(1)(C) of the
FD&C Act. The certification requirement in proposed Sec.  106.130(b)(4)
is a means to satisfy the statutory provision that a manufacturer
summarize test results and records to demonstrate compliance with
sections 412(b)(2)(A) and (b)(2)(B)(iii) of the FD&C Act. Such records
would be available for inspection by FDA. This requirement will be a
strong incentive to a manufacturer to confirm that the test results and
records that demonstrate compliance with section 412(b)(2)(A) and
(b)(2)(B)(iii) of the FD&C Act are complete based on the manufacturer's
established procedures. For these reasons, FDA is not revising proposed
Sec.  106.130(b)(4) in response to this comment, and the provision is
included in this interim final rule as proposed.
5. Administrative Procedures for Handling Verification Submissions
(Proposed Sec.  106.130(c))
    (Comment 349) One comment suggested modifying proposed Sec.
106.130(c), which states that a submission will not constitute written
verification under section 412(d)(2) of the FD&C Act when any data
prescribed by proposed Sec.  106.130(b) are lacking or are not set
forth so as to be readily understood and that, in such circumstances,
the Agency will notify the submitter that the verification is not
adequate. The comment suggested that this proposed provision be revised
to state that the Agency will notify the submitter within 5 working
days that the notice is not complete and asserted that without such
rapid notice, a manufacturer will not be able to market its product
with assurance that FDA found the submission acceptable. The comment
also recommended that the FDA develop a form for verifications that
will help in FDA's review of the sufficiency of these submissions.
    (Response) FDA disagrees with this comment. Although the Agency
fully intends to notify a manufacturer of the inadequacy of a
verification submission as promptly as possible, it is not reasonable
for FDA to commit to a specific time frame for such notice where it is
not compelled by statute and where, in some cases, competing priorities
or diminished resources may affect the Agency's ability to respond.
    Similarly, it is not necessary for the Agency to develop a form for
verification notifications because proposed Sec.  106.130 specifies the
information required in such a notification, and the Agency's review
will focus on those requirements. Development and clearance of such a
form would require Agency resources, and the comment did not
specifically identify the efficiencies or other benefits from the use
of the suggested form that would be expected to offset these
development and clearance costs. Accordingly, FDA is not revising
proposed Sec.  106.130(c) in response to this comment, and, with minor
editorial changes, the provision is included in this interim final rule
as proposed.

F. Submission Concerning a Change in Infant Formula That May Adulterate
the Product (Proposed Sec.  106.140)

    In 1996, the Agency proposed submission requirements to implement
section 412(d)(3) of the FD&C Act by issuing proposed Sec.  106.140.
Proposed Sec.  106.140 would have required that when a manufacturer
makes a change in the formulation or processing of an infant formula
that may affect whether the formula is adulterated under section 412(a)
of the FD&C Act, the manufacturer shall, before the first processing of
such formula, make a submission to FDA at the address given in proposed
Sec.  106.110(a).
    The Agency received several comments on proposed Sec.  106.140, and
responds below.
    (Comment 350) One comment expressed concern that infant formula
manufacturers may be reluctant to make minor changes in packaging
materials because they may think that these changes would require
additional stability testing of their formulas and additional
notifications to FDA under proposed Sec.  106.140. The comment
requested that FDA clarify that an infant formula manufacturer does not
need to conduct special stability testing or make a filing with FDA, in
accordance with proposed Sec.  106.140, when a packaging change is made
that clearly will not affect potential migration of packaging
components to the formula or the integrity of the packaging.
    (Response) FDA is not persuaded to make changes to the codified
based on this comment. Section 412(d)(3) of the FD&C Act provides that
a manufacturer is to make the determination as to whether a change in
the processing may affect whether the formula is adulterated. FDA
considers that a change in packaging constitutes a change in processing
for purposes of section 412(d)(3) of the FD&C Act. Therefore, if a
manufacturer determines that a packaging change may affect whether a
formula may be adulterated, a notification to FDA, in accordance with
Sec.  106.140 of the interim final rule, is required.
    Stability testing is governed by Sec.  106.91(b)(2) of the interim
final rule. Under that provision, a manufacturer is responsible for
ensuring that an infant formula satisfies the nutrient requirements of
the FD&C Act throughout the shelf life of the product. When a
manufacturer makes a packaging change for a specific formula, the
manufacturer must determine whether that change requires the
manufacturer to conduct additional stability testing to ensure that the
infant formula will contain the required nutrients throughout the shelf
life of the product. Moreover, the definition of ``major change''
includes a situation where there is a fundamental change in the type of
packaging used and such a change would make the formula a ``new''
infant formula for which a submission would be required under section
412(c) of the FD&C Act.

    Accordingly, FDA is not revising proposed Sec.  106.140 in response
to this comment, and the provision is included in this interim final
rule as proposed.
1. ``Before First Processing'' (BFP) Submissions (Proposed Sec.
106.140(a))
    (Comment 351) One comment suggested that proposed Sec.  106.140(a)
be revised to state that when a manufacturer makes a change in the
formulation or processing of a formula that the manufacturer or
responsible party determines may affect whether the formula is
adulterated under section 412(a) of the FD&C Act, the manufacturer
shall, before the first processing of such formula, make a submission
to the FDA. The comment asserted that this revision would clarify what
constitutes a ``minor change'' versus a ``major change.''
    (Response) Elsewhere in this preamble, FDA has declined to define
``minor change'' and reaffirms that decision now in response to this
comment. FDA notes that this comment suggests changes to proposed Sec.
106.140 that the comment believes would clarify what constitutes a
``major'' or ``minor'' change. However, the definition of ``major
change'' is addressed in section 412(c) of the FD&C Act and is defined
in Sec.  106.3 of the interim final rule. The comment does not explain
the utility or necessity of defining ``minor change,'' and such a
definition is not necessary. Also, unlike ``major change,'' for which
there are regulatory consequences (for example, filing a submission
under Sec.  106.120), there are no regulatory consequence identified in
the law or by the comment for a change that would be a ``minor
change.'' For this reason, FDA declines to define ``minor change'' in
response to this comment.
    (Comment 352) Another comment stated that under current practice,
infant formula manufacturers currently evaluate all changes to
formulation or processing of their infant formulas and if the
manufacturer determines the change may affect the nutrient content of
the formulation, the manufacturer notifies FDA. The comment asserted
that this requirement will increase the number of these submissions and
require additional personnel if a manufacturer is required to notify
FDA when any of the changes listed as examples of ``notifiable
changes'' in the preamble to the proposed rule occurs.
    (Response) Proposed Sec.  106.140 was designed to implement section
412(d)(3) of the FD&C Act, which requires that a manufacturer make a
submission to FDA before the first processing of a formula when the
manufacturer determines that a change in formulation or in the
processing of an infant formula may affect whether a formula is
adulterated under section 412(a) of the FD&C Act; the submission is
required by section 412(d)(3) of the FD&C Act to conform to the
requirements in section 412(d)(1) of the FD&C Act. A change that
constitutes a ``major change'' within the meaning of Sec.  106.3 of the
interim final rule is not the type of change that requires notification
under Sec.  106.140 because a ``major change'' makes a formula a ``new
infant formula'' and under section 412(c)(1) of the FD&C Act, the
manufacturer of a ``new infant formula'' must notify FDA of the change
in accordance with section 412(c)(1) of the FD&C Act and Sec.  106.120
of the interim final rule. The comment cited examples of changes that
FDA identified in the preamble to the proposed rule that could affect
whether a formula is adulterated and stated that increased submissions
and a need for additional personnel would be required, but the comment
did not explain why such examples are inconsistent with section
412(d)(3) of the FD&C Act. The examples FDA provided are of the type
that the Agency considers appropriate for submission under section
412(d)(3) of the FD&C Act and proposed Sec.  106.140(a).
    Based on the foregoing, FDA is not revising proposed Sec.
106.140(a) in response to these comments, and proposed Sec.  106.140(a)
is included in this interim final rule, with minor editorial changes,
as proposed.
    No comments were received requesting modification of proposed Sec.
106.140(b)(1). Thus, proposed Sec.  106.140(b)(1) is included in this
interim final rule as proposed.
2. Steps To Ensure That Formula Will Not Be Adulterated (Proposed Sec.
106.140(b)(2))
    (Comment 353) One comment suggested that proposed Sec.
106.140(b)(2), which requires that the submission explain why the
change in formulation or processing may affect whether the formula is
adulterated, also would require that the submission explain the steps
that will be taken to ensure that the formula will not be introduced
into interstate commerce unless it is not adulterated. The comment
asserted that this suggested requirement will enable FDA to receive a
more complete explanation of the change.
    (Response) FDA agrees with this comment. The Agency believes that
requiring a manufacturer to consider how it will resolve a question of
whether the formula is actually adulterated and to provide that
explanation to FDA will help to ensure that no adulterated formula will
enter distribution. Accordingly, FDA is revising Sec.  106.140(b)(2) in
response to this comment to require that the submission explain the
steps that will be taken to ensure that, before the formula is
introduced into interstate commerce, the formula will not be
adulterated.
3. Administrative Procedures (Proposed Sec.  106.140(c))
    (Comment 354) One comment suggested that proposed Sec.  106.140(c),
which provides that the Agency will notify the submitter if a notice is
not adequate because it does not meet the requirements of section
412(d)(3) of the FD&C Act, be revised to state that FDA will promptly
acknowledge receipt and notify the submitter if the notice is not
adequate because it does not meet the requirements of section 412(d)(3)
of the FD&C Act. The comment asserted that FDA should be required to
notify manufacturers within 1 week, or some other reasonable period of
time, if a submission is not adequate and that otherwise, a
manufacturer will not be able to market its product with assurance that
FDA found the submission to be adequate.
    (Response) FDA disagrees with this comment. The Agency's current
practice is to acknowledge the receipt of a new infant formula
submission. However, FDA declines to revise the interim final rule to
require such acknowledgment because future changes in Agency resources
and program priorities may make the current practice of acknowledgement
not feasible. Also, a manufacturer may make independent arrangements to
confirm FDA's receipt of its submission, such as by sending the
submission via U.S. mail with return receipt service.
    Similarly, although the Agency intends to notify a manufacturer of
the inadequacy of a submission made under Sec.  106.140 of the interim
final rule as promptly as possible, it is not reasonable for FDA to
commit to a specific time frame for such notice where such timing is
not compelled by statute and where, in some cases, competing priorities
or diminished resources may affect the Agency's ability to respond.
Thus, FDA is not persuaded to revise proposed Sec.  106.140(c) in
response to this comment, and this provision is included in this
interim final rule, with minor editorial changes, as proposed.
4. Infant Formulas Intended for Export Only
    (Comment 355) One comment requested clarification as to whether

infant formulas intended only for export must make the submission
concerning a change in infant formula that may adulterate the product.
The comment suggested that Sec.  106.140 include a paragraph (d) that
would state that the requirements of Sec.  106.140 do not apply to any
infant formula product legally exported under section 801(e) of the
FD&C Act.
    (Response) The Agency is not revising Sec.  106.140 in response to
this comment. Notification under Sec.  106.140 is only necessary when
the manufacturer makes a change to the formula that affects whether the
formula may be adulterated under section 412(a) of the FD&C Act. As
explained previously in this document, an infant formula intended for
export is not deemed to be adulterated under the FD&C Act, including
under section 412(a) of the FD&C Act, if it is in compliance with
section 801(e) of the FD&C Act. FDA would not consider an infant
formula intended for export that is in compliance with Sec.  106.120(c)
of the interim final rule and section 801(e) of the FD&C Act to be
adulterated under section 412(a) of the FD&C Act. Therefore, an infant
formula for export only that is in compliance with Sec.  106.120(c) of
the interim final rule and section 801(e) of the FD&C Act would not be
required to make any notification under Sec.  106.140 of the interim
final rule.
    However, the Agency advises that if a manufacturer makes a change
to its infant formula for export only that constitutes a ``major
change'' within the meaning of Sec.  106.3 of the interim final rule,
the manufacturer would be required to make a 90-day new infant formula
submission under Sec.  106.120 of the interim final rule. As stated in
earlier in this preamble, a new infant formula that is for export only
shall comply with Sec. Sec.  106.110 and 106.120 of the interim final
rule. Importantly, a manufacturer of a new infant formula for export
only may make an alternative submission under Sec.  106.120(c) of the
interim final rule for the submission requirements that relate to
whether the new infant formula is adulterated under section 412(a) of
the FD&C Act. However, if a manufacturer of a new infant formula for
export only elects to make a new infant formula submission under Sec.
106.120(b) of the interim final rule, the manufacturer would be
required to submit a verification submission under Sec.  106.130 of the
interim final rule and the submission concerning a change in infant
formula that may adulterate the product, if the formula was changed
under Sec.  106.140 of the interim final rule. When a manufacturer
makes a new infant formula submission under Sec.  106.120(b) of the
interim final rule, the Agency reviews the application using the
requirements in the FD&C Act and FDA's implementing regulations to
determine whether the formula meets these requirements and thus, is
eligible to be marketed in the United States. If a manufacturer elects
to have its formula reviewed as a formula to be marketed in the United
States, it must make all of the relevant submissions required by the
FD&C Act for such formulas.

G. Notification of an Adulterated or Misbranded Infant Formula
(Proposed Sec.  106.150)

    In the 1996 proposal, FDA proposed to recodify Sec.  106.120(b) in
subpart G and to designate the recodified provision as Sec.  106.150.
The proposed recodification included several minor editorial changes to
the text of current Sec.  106.120(b).
    The Agency received several comments on this proposed
recodification, and responds below.
    (Comment 356) One comment suggested a modification of proposed
Sec.  106.150(a)(2), which would have required that a manufacturer
promptly notify FDA if an infant formula that the manufacturer has
processed and that has left the manufacturer's control may be
adulterated or misbranded. The comment suggested adding the following:
``In the case of 'adulteration' based on a failure to follow CGMP, the
failure must be of such a nature as to reasonably call into question
the suitability of the formula. Notification shall not be required for
minor or technical misbranding.'' In support of this suggestion, the
comment asserted that a violation of the infant formula CGMP, no matter
how minor or inconsequential, will constitute a ``technical
adulteration or misbranding'' of the product, that formula
manufacturers are of the only members of the food industry compelled to
notify FDA when a distributed product is or may be ``adulterated'' or
``misbranded,'' and thus, it is critical to weigh each proposed
regulation for the consequences of a finding of ``adulteration'' or
``misbranding'' to ensure that such regulations are appropriate. The
comment concluded that only adulteration of public health significance
and only significant or actionable misbranding should trigger
notification.
    (Response) FDA disagrees that with this comment. Proposed Sec.
106.150, and its predecessor, current Sec.  106.120(b), implement
section 412(e)(1)(B) of the FD&C Act. This statutory provision requires
a formula manufacturer to notify the Secretary (and by delegation, FDA)
when the manufacturer has knowledge which reasonably supports the
conclusion that an infant formula which has been processed by the
manufacturer and which has left an establishment subject to the control
of the manufacturer may not provide the nutrients required by section
412(i) of the FD&C Act or ``may be otherwise adulterated or
misbranded.'' Section 412(e)(1) of the FD&C Act provides that the
Secretary (and by delegation, FDA), and not the manufacturer, shall
determine whether the released infant formula presents a risk to human
health. Thus, it is incumbent upon the FDA to evaluate the public
health risk that may be associated with an adulterated or misbranded
infant formula, and the modification requested in this comment would be
inconsistent with the governing statutory provision.
    In addition, FDA disagrees that Sec.  106.150(a) should be modified
so that notification of adulteration based on a failure to follow CGMP
need only be made if the failure to follow CGMP reasonably calls into
question the suitability of the formula. A failure to follow CGMP
indicates that a manufacturer's process is not under appropriate
control, and thus, a manufacturer should promptly and fully address
such failure following discovery. Only if FDA is aware of the finding
of a breach of infant formula CGMP can the Agency appropriately monitor
the manufacturer and ensure that further problems do not develop.
Moreover, as noted elsewhere in this preamble, safety considerations
are of unique importance with infant formula because such formula is
intended to be the sole source of nutrition for infants during the
early period of significant development and growth. Therefore, it is
incumbent upon the Agency to evaluate the public health risks that may
be associated with an adulterated or misbranded infant formula.
    FDA recognizes that some infant formula CGMP failures may not have
public health consequences. However, the Agency must be made aware of
all formulas that have left the control of the manufacturer that may be
adulterated or misbranded so that FDA can discharge its obligation
under section 412(e)(1) of the FD&C Act. Accordingly, FDA declines to
modify proposed Sec.  106.150 in response to this comment.
    The Agency is, however, modifying Sec.  106.150(b) to update the
contact information for submission of a notification of an adulterated
or misbranded infant formula. Thus, Sec.  106.150(b) of the interim
final rule

requires, in part, that the manufacturer ``shall promptly send written
confirmation of the notification to the Food and Drug Administration,
Center for Food Safety and Applied Nutrition, Office of Compliance,
Division of Enforcement (HFS-605), Recall Coordinator, 5100 Paint
Branch Parkway, College Park, MD 20740, and to the appropriate FDA
district office.''

H. Incorporation by Reference

    Certain material is incorporated by reference in the interim final
rule with the approval of the Director of the Federal Register. For
purposes of clarity and ease of reference, FDA has gathered in a single
place in the interim final rule (Sec.  106.160) a list of the material
that is incorporated by reference and information about how these
materials may be obtained from their source.

XI. Conforming Amendments to Part 107

    In 1996, FDA proposed revisions to the regulations in part 107 to
reflect the changes made by the 1986 amendments and the regulations
that FDA was proposing to adopt in part 106. The Agency also proposed
certain editorial changes. FDA received no comments on the proposed
revisions to part 107.
    As explained elsewhere in this preamble, the interim final rule
revises certain proposed provisions in part 106, which revisions were
made in response to comments or for other reasons. Also, due to the
passage of time, additional technical changes to part 107 are necessary
to update Agency addresses and telephone numbers. Accordingly, as
included in this interim final rule, part 107 reflects the revisions
proposed in 1996 modified by additional technical changes and changes
required for consistency with the provisions of part 106.

XII. Environmental Impact

    The Agency has determined under 21 CFR 25.30(j) and 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.

XIII. Federalism

    FDA has analyzed this interim final rule in accordance with the
principles set forth in Executive Order 13132. FDA has 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, the Agency concludes
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.

XIV. Regulatory Impact Analysis for Interim Final Rule

    FDA has examined the impacts of this interim 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). We have developed a detailed
Regulatory Impact Analysis (RIA) that presents the benefits and costs
of this interim final rule (Ref. 92) which is available at http://www.regulations.gov (enter Docket No. FDA-1995-N-0036). The full
economic impact analyses of FDA regulations are no longer (as of April
2012) published in the Federal Register but are submitted to the docket
and are available at http://www.regulations.gov. We believe that the
interim final 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. According to our analysis, we believe that the
interim 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 $141 million, using the most current (2012) Implicit
Price Deflator for the Gross Domestic Product. FDA does not expect this
interim final rule to result in any 1-year expenditure that would meet
or exceed this amount.
    The analyses that we have performed to examine the impacts of this
interim final rule under Executive Order 12866, Executive Order 13563,
the Regulatory Flexibility Act, and the Unfunded Mandates Reform Act of
1995 are included in the RIA (Ref. 92).
    We included a Summary of the Economic Analysis of the Proposed Rule
in the RIA (Ref. 92. We received comments on our analysis of the
impacts presented in those sections, and the RIA (Ref. 92) contains our
responses to those comments.

XV. Paperwork Reduction Act of 1995

    This interim final rule contains information collection
requirements 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) (the PRA). A description of these provisions with estimates of
the annual reporting, recordkeeping, and third-party disclosure burden
are included in the RIA in section IV, entitled ``Paperwork Reduction
Act of 1995'' (Ref. 92). 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.
    In the July 9, 1996, proposed rule, FDA included an analysis of the
information collection provisions of the proposal under the PRA and
requested comments on four questions relevant to that analysis (61 FR
at 36205-36206). Subsequently, in 2003, the Agency reopened the comment
period to update comments and to receive any new information on all
issues, including on the PRA analysis (68 FR 22341). In response to
these requests, FDA received no comments specifically referring to the
Agency's 1996 PRA analysis or otherwise referring to the PRA. FDA did
receive comments on the substantive provisions of the proposed rule,
including comments on the proposed recordkeeping and other provisions
of the proposal that would result in information collections. FDA has
summarized and responded to these comments in the RIA (Ref. 92).
    As noted, the 1996 proposal included a PRA analysis. FDA is re-
estimating the burden of this interim final rule using current burden
analysis methodology. The Agency invites comments on new issues
relating to 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.
    In compliance with the PRA, FDA has submitted the information
collection provisions of this interim final rule to OMB for review.
Prior to the effective date of this interim final rule, FDA will
publish a notice in the Federal Register announcing OMB's decision to
approve, modify, or disapprove the information collection provisions in
this interim final rule. An Agency may not conduct or sponsor, and a
person is not required to respond to, a collection of information
unless it displays a currently valid OMB control number.

XVI. Comments

    The requirements in this interim final rule will be in effect on
July 10, 2014. FDA invites the public to comment on this interim final
rule. Comments submitted in response to this interim final rule should
be limited to those that present new issues or new information.
Comments previously submitted to the Division of Dockets Management
have been considered and addressed in this interim final rule and
should not be resubmitted.
    Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) either electronic or written comments regarding this
interim final rule. 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.

XVII. References

    The following references have been placed on display in the
Division of Dockets Management, 5630 Fishers Lane, Rm. 1061, Rockville,
MD 20852, and may be seen by interested persons between 9 a.m. and 4
p.m., Monday through Friday. We have verified all the Web site
addresses in the References section, but we are not responsible for any
subsequent changes to the Web sites after this document publishes in
the Federal Register.

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List of Subjects

21 CFR Part 106

    Food grades and standards, Infants and children, Incorporation by
reference, Nutrition, Reporting and recordkeeping requirements.

21 CFR Part 107

    Food labeling, Infants and children, Nutrition, Reporting and
recordkeeping, 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 parts
106 and 107 are amended as follows:

0
1. Revise part 106 to read as follows:

PART 106--INFANT FORMULA REQUIREMENTS PERTAINING TO CURRENT GOOD
MANUFACTURING PRACTICE, QUALITY CONTROL PROCEDURES, QUALITY
FACTORS, RECORDS AND REPORTS, AND NOTIFICATIONS

Subpart A--General Provisions
Sec.
106.1 Status and applicability of the regulations in part 106.
106.3 Definitions.
Subpart B--Current Good Manufacturing Practice
106.5 Current good manufacturing practice.
106.6 Production and in-process control system.
106.10 Controls to prevent adulteration by workers.
106.20 Controls to prevent adulteration caused by facilities.
106.30 Controls to prevent adulteration caused by equipment or
utensils.
106.35 Controls to prevent adulteration due to automatic (mechanical
or electronic) equipment.
106.40 Controls to prevent adulteration caused by ingredients,
containers, and closures.
106.50 Controls to prevent adulteration during manufacturing.
106.55 Controls to prevent adulteration from microorganisms.
106.60 Controls to prevent adulteration during packaging and
labeling of infant formula.
106.70 Controls on the release of finished infant formula.
106.80 Traceability.
106.90 Audits of current good manufacturing practice.
Subpart C--Quality Control Procedures
106.91 General quality control.
106.92 Audits of quality control procedures.
Subpart D--Conduct of Audits
106.94 Audit plans and procedures.
Subpart E--Quality Factors for Infant Formulas
106.96 Requirements for quality factors for infant formulas.
Subpart F--Records and Reports
106.100 Records.
Subpart G--Registration, Submission, and Notification Requirements
106.110 New infant formula registration.
106.120 New infant formula submission.
106.121 Quality factor assurances for infant formulas.
106.130 Verification submission.
106.140 Submission concerning a change in infant formula that may
adulterate the product.
106.150 Notification of an adulterated or misbranded infant formula.
106.160 Incorporation by reference.

    Authority:  21 U.S.C. 321, 342, 350a, 371.

Subpart A--General Provisions

Sec.  106.1  Status and applicability of the regulations in part 106.

    (a) The criteria set forth in subparts B, C, and D of this part
prescribe the steps that manufacturers shall take under section
412(b)(2) and (b)(3) of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 350a(b)(2) and (b)(3)) in processing infant formula. If the
processing of the formula does not comply with any regulation in
subparts B, C, or D of this part, the formula will be deemed to be
adulterated under section 412(a)(3) of the Federal Food, Drug, and
Cosmetic Act.
    (b) The criteria set forth in subpart E of this part prescribe the
requirements for quality factors that infant formula shall meet under
section 412(b)(1) of the Federal Food, Drug, and Cosmetic Act. If the
formula fails to comply with any regulation in subpart E of this part,
it will be deemed to be adulterated under section 412(a)(2) of the
Federal Food, Drug, and Cosmetic Act.
    (c) The criteria set forth in subpart F of this part prescribe
records requirements for quality factors under section 412(b)(1) of the
Federal Food, Drug, and Cosmetic Act and for good manufacturing
practices and quality control procedures, including distribution and
audit records, under section 412(b)(2). If an infant formula
manufacturer fails to comply with the quality factor record
requirements in subpart F of this part with respect to an infant
formula, the formula will be deemed to be adulterated under section
412(a)(2) of the Federal Food, Drug, and Cosmetic Act. If an infant
formula manufacturer fails to comply with the good manufacturing
practices or quality control procedures record requirements in subpart
F of this part with respect to an infant formula, the infant formula
will be deemed to be adulterated under section 412(a)(3) of the Federal
Food, Drug, and Cosmetic Act. The criteria set forth in subpart F of
this part also implement record retention requirements under section
412(b)(4) of the Federal Food, Drug, and Cosmetic Act. Failure to
comply with any regulation in subpart F of this part is a violation of
section 301(e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
331(e)).
    (d) The criteria set forth in subpart G of this part describe, in
part, certain good manufacturing practices, quality control procedures,
and quality factor records requirements under section 412(b)(1) and
(b)(2) of the Federal Food, Drug and Cosmetic Act. If an infant formula
manufacturer fails to comply with such records requirements with
respect to an infant formula, the infant formula will be deemed to be
adulterated under section 412(a)(2) or (a)(3) of the Federal Food,
Drug, and Cosmetic Act, as applicable. The criteria set forth in
subpart G of this part also describe the circumstances in which an
infant formula manufacturer is required to register with, submit to, or
notify the Food and Drug Administration, and the content of a
registration, submission, or notification, under section 412(c), (d),
and (e) of the Federal Food, Drug, and Cosmetic Act. Failure to comply
with any regulation in subpart G of this part is a violation of section
301(s) of the Federal Food, Drug, and Cosmetic Act.

Sec.  106.3  Definitions.

    The definitions in this section and the definitions contained in
section 201 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321)
shall apply to infant formula requirements in 21 CFR parts 106 and 107
of this chapter.
    Eligible infant formula means an infant formula that could have
been or was lawfully distributed in the United States on May 12, 2014.
    Final product stage means the point in the manufacturing process,
before distribution of an infant formula, at which the infant formula
is homogeneous and is not subject to further degradation due to
processing.
    Indicator nutrient means a nutrient whose concentration is measured
during the manufacture of an infant formula to confirm complete
addition and uniform distribution of a premix or other substance of
which the indicator nutrient is a part.
    Infant means a person not more than 12 months of age.
    Infant formula means 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.
    In-process production aggregate means a combination of ingredients
at any point in the manufacturing process before packaging.
    Major change in an infant formula means any new formulation, or any
change of ingredients or processes where experience or theory would
predict a possible significant adverse impact on levels of nutrients or
bioavailability of nutrients, or any

change that causes an infant formula to differ fundamentally in
processing or in composition from any previous formulation produced by
the manufacturer. Examples of infant formulas deemed to differ
fundamentally in processing or in composition include:
    (1) Any infant formula produced by a manufacturer who is entering
the U.S. market;
    (2) Any infant formula powder processed and distributed by a
manufacturer who previously only produced liquids (or vice versa);
    (3) Any infant formula having a significant revision, addition, or
substitution of a macronutrient (i.e., protein, fat, or carbohydrate),
with which the manufacturer has not had previous experience;
    (4) Any infant formula manufactured on a new processing line or in
a new plant;
    (5) Any infant formula manufactured containing a new constituent
not listed in section 412(i) of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 350a(i)), such as taurine or L-carnitine;
    (6) Any infant formula processed by a manufacturer on new equipment
that utilizes a new technology or principle (e.g., from terminal
sterilization to aseptic processing); or
    (7) An infant formula for which there has been a fundamental change
in the type of packaging used (e.g., changing from metal cans to
plastic pouches).
    Manufacturer means a person who prepares, reconstitutes, or
otherwise changes the physical or chemical characteristics of an infant
formula or packages or labels the product in a container for
distribution. The term ``manufacturer'' does not include a person who
prepares, reconstitutes, or mixes infant formula exclusively for an
infant under his/her direct care or the direct care of the institution
employing such person.
    Microorganisms means yeasts, molds, bacteria, and viruses and
includes, but is not limited to, species having public health
significance.
    New infant formula means:
    (1) An infant formula manufactured by a person that has not
previously manufactured an infant formula, and
    (2) An infant formula manufactured by a person that has previously
manufactured infant formula and in which there is a major change in
processing or formulation from a current or any previous formulation
produced by such manufacturer, or which has not previously been the
subject of a submission under section 412(c) of the Federal Food, Drug,
and Cosmetic Act for the U.S. market.
    Nutrient means any vitamin, mineral, or other substance or
ingredient that is required in accordance with the ``Nutrients'' table
set out in section 412(i)(1) of the Federal Food, Drug, and Cosmetic
Act or by regulations issued under section 412(i)(2) or that is
identified as essential for infants by the Food and Nutrition Board of
the Institute of Medicine through its development of a Dietary
Reference Intake, or that has been identified as essential for infants
by the Food and Drug Administration through a Federal Register
publication.
    Nutrient premix means a combination of ingredients containing two
or more nutrients received from a supplier or prepared by an infant
formula manufacturer.
    Production aggregate means a quantity of product, or, in the case
of an infant formula produced by continuous process, a specific
identified amount produced in a unit of time, that is intended to have
uniform composition, character, and quality, within specified limits,
and is produced according to a master manufacturing order.
    Production unit means a specific quantity of an infant formula
produced during a single cycle of manufacture that has uniform
composition, character, and quality, within specified limits.
    Production unit number or production aggregate number means any
distinctive combination of letters, numbers, symbols, or any
combination of them, from which the complete history of the
manufacture, processing, packing, holding, and distribution of a
production aggregate or a production unit of infant formula can be
determined.
    Quality factors means those factors necessary to demonstrate the
bioavailability and safety of the infant formula, as prepared for
market and when fed as the sole source of nutrition, including the
bioavailability of individual nutrients in the formula, to ensure the
healthy growth of infants.
    Representative sample means a sample that consists of a number of
units that are drawn based on rational criteria, such as random
sampling, and intended to ensure that the sample accurately portrays
the material being sampled.
    Shall is used to state mandatory requirements.

Subpart B--Current Good Manufacturing Practice

Sec.  106.5  Current good manufacturing practice.

    (a) The regulations set forth in this subpart define the minimum
current good manufacturing practices that are to be used in, and the
facilities or controls that are to be used for, the manufacture,
processing, packing, or holding of an infant formula. Compliance with
these provisions is necessary to ensure that such infant formula
provides the nutrients required under Sec.  107.100 of this chapter and
is manufactured in a manner designed to prevent its adulteration. A
liquid infant formula that is a thermally processed low-acid food
packaged in a hermetically sealed container is also subject to the
regulations in part 113 of this chapter, and an infant formula that is
an acidified food, as defined in Sec.  114.3(b) of this chapter, is
also subject to the regulations in part 114 of this chapter.
    (b) The failure to comply with any regulation in this subpart in
the manufacture, processing, packing, or holding of an infant formula
shall render such infant formula adulterated under section 412(a)(3) of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(a)(3)); the
failure to comply with any regulation in part 113 of this chapter in
the manufacture, processing, packing, or holding of a liquid infant
formula shall render such infant formula adulterated under section
412(a)(3); and the failure to comply with any regulation in part 114 of
this chapter in the manufacture, processing, packing, or holding of an
infant formula that is an acidified food shall render such infant
formula adulterated under section 412(a)(3).

Sec.  106.6  Production and in-process control system.

    (a) A manufacturer shall conform to the requirements of this
subpart by implementing a system of production and in-process controls.
This production and in-process control system shall cover all stages of
processing, from the receipt and acceptance of the raw materials,
ingredients, and components through the storage and distribution of the
finished product and shall be designed to ensure that all the
requirements of this subpart are met.
    (b) The production and in-process control system shall be set out
in a written plan or set of procedures that is designed to ensure that
an infant formula is manufactured in a manner that will prevent
adulteration of the infant formula.
    (c) At any point, step, or stage in the production process where
control is necessary to prevent adulteration, a manufacturer shall:
    (1) Establish specifications to be met;
    (2) Monitor the production and in-process control point, step, or
stage;

    (3) Establish a corrective action plan for use when a specification
established in accordance with paragraph (c)(1) of this section is not
met;
    (4) Review the results of the monitoring required by paragraph
(c)(2) of this section, and review and evaluate the public health
significance of any deviation from specifications that have been
established in accordance with paragraph (c)(1) of this section. For
any specification established in accordance with paragraph (c)(1) of
this section that a manufacturer fails to meet, an individual qualified
by education, training, or experience shall conduct a documented review
and shall make a material disposition decision to reject the affected
article, to reprocess or otherwise recondition the affected article, or
to approve and release the article for use or distribution; and
    (5) Establish recordkeeping procedures, in accordance with Sec.
106.100(e)(3), that ensure that compliance with the requirements of
this section is documented.
    (d) Any article that fails to meet a specification established in
accordance with paragraph (c)(1) of this section shall be controlled
under a quarantine system designed to prevent its use pending the
completion of a documented review and material disposition decision.

Sec.  106.10  Controls to prevent adulteration by workers.

    (a) A manufacturer shall employ sufficient personnel, qualified by
education, training, or experience, to perform all operations,
including all required recordkeeping, in the manufacture, processing,
packing, and holding of each infant formula and to supervise such
operations to ensure that the operations are correctly and fully
performed.
    (b) Personnel working directly with infant formula, infant formula
raw materials, infant formula packaging, or infant formula equipment or
utensil contact surfaces shall practice good personal hygiene to
protect the infant formula against contamination. Good personal hygiene
includes:
    (1) Wearing clean outer garments and, as necessary, protective
apparel such as head, face, hand, and arm coverings; and
    (2) Washing hands thoroughly in a hand washing facility with soap
and running water at a suitable temperature before starting work, after
each absence from the work station, and at any other time when the
hands may become soiled or contaminated.
    (c) Any person who reports that he or she has, or appears by
medical examination or supervisory observation to have, an illness,
open lesion (including boils, sores, or infected wounds), or any other
source of microbial contamination that creates a reasonable possibility
that the safety of an infant formula may be adversely affected, shall
be excluded from direct contact with ingredients, containers, closures,
in-process materials, equipment, utensils, and infant formula product
until the condition is corrected or determined by competent medical
personnel not to jeopardize the safety of the infant formula.

Sec.  106.20  Controls to prevent adulteration caused by facilities.

    (a) Buildings used in the manufacture, processing, packing, or
holding of infant formula shall be maintained in a clean and sanitary
condition and shall have space for the separation of incompatible
operations, such as the handling of raw materials, the manufacture of
the product, and packaging and labeling operations.
    (b) Separate areas or another system of separation, such as a
computerized inventory control, a written card system, or an automated
system of segregation, shall be used for holding raw materials, in-
process materials, and final infant formula product at the following
times:
    (1) Pending release for use in infant formula production or pending
release of the final product;
    (2) After rejection for use in, or as, infant formula; and
    (3) After release for use in infant formula production or after
release of the final product.
    (c) Lighting shall allow easy identification of raw materials,
packaging, labeling, in-process materials, and finished products that
have been released for use in infant formula production and shall
permit the easy reading of instruments and controls necessary in
processing, packaging, and laboratory analysis. Any lighting fixtures
directly over or adjacent to exposed raw materials, in-process
materials, or bulk (unpackaged) finished product shall be protected to
prevent glass from contaminating the product in the event of breakage.
    (d) A manufacturer shall provide adequate ventilation or control
equipment to minimize odors and vapors (including steam and noxious
fumes) in areas where they may contaminate the infant formula; and
shall minimize the potential for contamination of raw materials, in-
process materials, final product infant formula, packing materials, and
infant formula-contact surfaces, through the use of appropriate
measures, which may include the use of air filtration.
    (e) All rodenticides, insecticides, fungicides, fumigating agents,
and cleaning and sanitizing agents shall be stored and used in a manner
that protects against contamination of infant formula.
    (f) Potable water used in the manufacture of infant formula shall
meet the standards prescribed in the Environmental Protection Agency's
(EPA's) Primary Drinking Water regulations in 40 CFR part 141, except
that the water used in infant formula manufacturing shall not be
fluoridated or shall be defluoridated to a level as low as possible
prior to use.
    (1) The water shall be supplied under continuous positive pressure
in a plumbing system that is free of defects that could contaminate an
infant formula.
    (2) A manufacturer shall test representative samples of the potable
water drawn at a point in the system at which the water is in the same
condition that it will be when it is used in infant formula
manufacturing.
    (3) A manufacturer shall conduct the tests required by paragraph
(f)(2) of this section with sufficient frequency to ensure that the
water meets the EPA's Primary Drinking Water Regulations but shall not
conduct these tests less frequently than annually for chemical
contaminants, every 4 years for radiological contaminants, and weekly
for bacteriological contaminants.
    (4) A manufacturer shall make and retain records, in accordance
with Sec.  106.100(f)(1), of the frequency and results of testing of
the water used in the production of infant formula.
    (g) There shall be no backflow from, or cross-connection between,
piping systems that discharge waste water or sewage and piping systems
that carry water for infant formula manufacturing.
    (h) Only culinary steam shall be used at all direct infant formula
product contact points. Culinary steam shall be in compliance with the
3-A Sanitary Standards, No. 60903, which is incorporated by reference
at Sec.  106.160. Boiler water additives in the steam shall be used in
accordance with Sec.  173.310 of this chapter.
    (i) Each infant formula manufacturing site shall provide its
employees with readily accessible toilet facilities and hand washing
facilities that include hot and cold water, soap or detergent, single-
service towels or air dryers in toilet facilities. These facilities
shall be maintained in good repair and in a sanitary condition at all
times. These facilities shall provide for proper disposal of the
sewage. Doors to the

toilet facility shall not open into areas where infant formula
ingredients, containers, or closures are stored, or where infant
formula is processed or stored.

Sec.  106.30  Controls to prevent adulteration caused by equipment or
utensils.

    (a) A manufacturer shall ensure that equipment and utensils used in
the manufacture, processing, packing, or holding of an infant formula
are of appropriate design and are installed to facilitate their
intended function and their cleaning and maintenance.
    (b) A manufacturer shall ensure that equipment and utensils used in
the manufacture, processing, packing, or holding of an infant formula
are constructed so that surfaces that contact ingredients, in-process
materials, or infant formula are made of nontoxic materials and are not
reactive or absorptive. A manufacturer shall ensure that such equipment
and utensils are designed to be easily cleanable and to withstand the
environment of their intended use and that all surfaces that contact
ingredients, in-process materials, or infant formula are cleaned and
sanitized, as necessary, and are maintained to protect infant formula
from being contaminated by any source. All sanitizing agents used on
such equipment and utensils that are regulated as pesticide chemicals
under 21 U.S.C. 346a(a) shall comply with the Environmental Protection
Agency's regulations established under such section, and all other such
sanitizers shall comply with all applicable Food and Drug
Administration laws and regulations.
    (c) A manufacturer shall ensure that any substance, such as a
lubricant or a coolant, that is required for operation of infant
formula manufacturing equipment and which would render the infant
formula adulterated if such substance were to come in contact with the
formula, does not come in contact with formula ingredients, containers,
closures, in-process materials, or with infant formula product during
the manufacture of an infant formula.
    (d) A manufacturer shall ensure that each instrument used for
measuring, regulating, or controlling mixing time and speed,
temperature, pressure, moisture, water activity, or other parameter at
any point, step, or stage where control is necessary to prevent
adulteration of an infant formula during processing is accurate, easily
read, properly maintained, and present in sufficient number for its
intended use.
    (1) The instruments and controls shall be calibrated against a
known reference standard at the time of or before first use and
thereafter at routine intervals, as specified in writing by the
manufacturer of the instrument or control, or as otherwise deemed
necessary to ensure the accuracy of the instrument or control. The
known reference standard shall be certified for accuracy at the
intervals specified in writing by the manufacturer of the instrument or
control, or at routine intervals otherwise deemed necessary to ensure
the accuracy of the instrument or control. A manufacturer shall make
and retain records of the calibration activities in accordance with
Sec.  106.100(f)(2).
    (2) Instruments and controls that cannot be adjusted to agree with
the reference standard shall be repaired or replaced.
    (3) If calibration of an instrument shows a failure to meet a
specification for a point where control is deemed necessary to prevent
adulteration of infant formula product, a written evaluation of all
affected product, and of any actions that need to be taken with respect
to that product, shall be made, in accordance with Sec.  106.100(f)(2).
    (e) The following provisions apply to thermal processing and cold
storage of infant formulas:
    (1) Equipment and procedures for thermal processing of infant
formula packaged in hermetically sealed containers shall conform to the
requirements in 21 CFR parts 108 and 113.
    (2)(i) Except as provided in paragraph (e)(2)(ii) of this section,
a manufacturer shall maintain all areas of cold storage at a
temperature of 40 [deg]F (4.4 [deg]C) or below.
    (ii) A manufacturer may maintain a cold storage area for an in-
process infant formula or for a final infant formula at a temperature
not to exceed 45 [deg]F (7.2 [deg]C) for a defined period of time
provided that the manufacturer has scientific data and other
information to demonstrate that:
    (A) Compliance with paragraph (e)(2)(i) of this section would have
an adverse effect on the quality of the in-process or the final infant
formula through, e.g., destabilization or loss of homogeneity; and
    (B) The time and temperature conditions of such storage are
sufficient to ensure that there is no significant growth of
microorganisms of public health significance during the period of
storage of the in-process or final infant formula product.
    (3)(i) Cold storage compartments and thermal processing equipment
shall be equipped with easily readable, accurate temperature-indicating
devices.
    (ii) A manufacturer shall ensure that the temperature of each cold
storage compartment is maintained by:
    (A) Monitoring the temperature of the cold storage compartment on a
temperature-indicating device and recording this temperature in a
record with such frequency as is necessary to ensure that temperature
control is maintained;
    (B) Equipping the cold storage compartment with one or more
temperature-recording devices that will reflect, on a continuing basis,
the true temperature, within the compartment;
    (C) Equipping the cold storage compartment with a high temperature
alarm that has been validated to function properly and recording the
temperature in a record with such frequency as is necessary to ensure
that temperature control is maintained; or
    (D) Equipping the cold storage compartment with a maximum-
indicating thermometer that has been validated to function properly and
recording this temperature in a record with such frequency as is
necessary to ensure that temperature control is maintained.
    (iii) A manufacturer shall, in accordance with Sec.  106.100(f)(3),
make and retain records of the temperatures recorded in compliance with
Sec.  106.30(e)(3)(ii).
    (4) When a manufacturer uses a temperature-recording device for a
cold storage compartment, such device shall not read lower than the
reference temperature-indicating device.
    (5) A manufacturer shall monitor the temperature in thermal
processing equipment at points where temperature control is necessary
to prevent adulteration. Such monitoring shall be at such frequency as
is required by regulation or is necessary to ensure that temperature
control is maintained.
    (f) A manufacturer shall ensure that equipment and utensils used in
the manufacture of infant formula are cleaned, sanitized, and
maintained at regular intervals to prevent adulteration of the infant
formula.
    (1) An individual qualified by education, training, or experience
to conduct such a review shall review all cleaning, sanitizing, and
maintenance to ensure that it has been satisfactorily completed.
    (2) A manufacturer shall make and retain records on equipment
cleaning, sanitizing, and maintenance, in accordance with Sec.
106.100(f)(4).
    (g) A manufacturer shall ensure that compressed air or other gases
that are mechanically introduced into infant formula, that are used to
clean any equipment, or that come into contact

with any other surface that contacts ingredients, in-process materials,
or infant formula product are treated in such a way that their use will
not contaminate the infant formula with unlawful or other chemical,
physical, or microbiological contaminants. When compressed gases are
used at product filling machines to replace air removed from the
headspace of containers, a manufacturer shall install, as close as
practical to the end of the gas line that feeds gas into the space, a
filter capable of retaining particles 0.5 micrometer or smaller.

Sec.  106.35  Controls to prevent adulteration due to automatic
(mechanical or electronic) equipment.

    (a) For the purposes of this section:
    (1) ``Hardware'' means all automatic equipment, including
mechanical and electronic equipment (such as computers), that is used
in production or quality control of infant formula.
    (2) ``Software'' means any programs, procedures, rules, and
associated documentation used in the operation of a system.
    (3) ``System'' means a collection of components (including software
and hardware) organized to accomplish a specific function or set of
functions in a specified environment.
    (4) ``Validation'' means establishing documented evidence that
provides a high degree of assurance that a system will consistently
produce a product meeting its predetermined specifications and quality
characteristics.
    (b) All systems shall be designed, installed, tested, and
maintained in a manner that will ensure that they are capable of
performing their intended function and of producing or analyzing infant
formula in accordance with this subpart and subpart C of this part.
    (1) A manufacturer shall ensure that hardware that is capable of
being calibrated is routinely calibrated according to written
procedures, and that all hardware is routinely inspected and checked
according to written procedures.
    (2) A manufacturer shall check and document the accuracy of input
into, and output generated by, any system used in the production or
quality control of an infant formula to ensure that the infant formula
is not adulterated. The degree and frequency of input/output
verification shall be based on the complexity and reliability of the
system and the level of risk associated with the safe operation of the
system.
    (3) A manufacturer shall ensure that each system is validated prior
to the release for distribution of any infant formula manufactured
using the system.
    (4) A manufacturer shall ensure that any system that is modified is
revalidated following the modification and prior to the release for
distribution of any infant formula manufactured using the modified
system. All modifications to software shall be made by a designated
individual and shall be checked by the infant formula manufacturer to
ensure that infant formula that is produced or analyzed using the
modified software complies with this subpart and with subpart C of this
part.
    (c) A manufacturer shall make and retain records, in accordance
with Sec.  106.100(f)(5), concerning mechanical or electronic
equipment.

Sec.  106.40  Controls to prevent adulteration caused by ingredients,
containers, and closures.

    (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 Federal Food, Drug, and
Cosmetic Act; that is, a substance is used in accordance with the
Agency's food additive regulations, is generally recognized as safe
(GRAS) for such use, or is authorized by a prior sanction.
    (b) Infant formula containers and closures shall not be reactive or
absorptive so as to affect the safety of the infant formula. The
following substances may be used as packaging material that comes in
contact with an infant formula:
    (1) A food additive that is the subject of a regulation issued
under section 409(c) of the Federal Food, Drug, and Cosmetic Act (21
U.S.C. 348(c)) and is used consistent with the conditions of use of
that regulation;
    (2) A food contact substance that is the subject of an effective
notification under section 409(h) of the Federal Food, Drug, and
Cosmetic Act and is used consistent with the conditions of use in that
notification;
    (3) A substance that is exempt from regulation as a food additive
under Sec.  170.39 of this chapter and its use conforms to the use
identified in the exemption letter;
    (4) A substance that is generally recognized as safe for use in or
on infant formula or for use in infant formula packaging;
    (5) A substance the use of which is authorized by a prior sanction
from the Food and Drug Administration or from the U.S. Department of
Agriculture; and
    (6) A substance that is not a food additive within the meaning of
section 201(s) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
321(s)) because the substance is not reasonably expected to become a
component of food or otherwise affect the characteristics of food.
    (c) Ingredients, containers, and closures used in the manufacture
of infant formula shall be identified with a lot number to be used in
recording their disposition.
    (d) A manufacturer shall develop written specifications for
ingredients, containers, and closures used in manufacturing infant
formula and shall develop and follow written procedures to determine
whether all ingredients, containers, and closures meet these
specifications. When any specification is not met, an individual
qualified by education, training, or experience shall conduct a
documented review, shall determine whether a failure to meet such a
specification could result in an adulterated infant formula, and shall
make and document a material disposition decision to reject the
ingredient, container, or closure or the affected infant formula; to
reprocess or otherwise recondition the ingredient, container, or
closure or the affected infant formula; or to approve and release the
ingredient, container, or closure or the affected infant formula for
use.
    (e) Ingredients, containers, and closures shall be stored in
separate areas or separated by a system of segregation, such as a
computerized inventory control, a written card system, or an automated
system of segregation, clearly designated for materials pending release
for use; materials released for use; or materials rejected for use in
infant formula production.
    (1) Any lot of an ingredient, a container, or a closure that does
not meet the manufacturer's specifications shall be quarantined under a
system designed to prevent its use in the manufacture of infant formula
until an individual qualified by education, training, or experience has
conducted a documented review, has determined whether such failure
could result in an adulterated infant formula, and has made and
documented a material disposition decision to reject the ingredient,
container, closure, or the affected infant formula; to reprocess or
otherwise recondition the ingredient, container, closure, or the
affected infant formula; or to approve and release the ingredient,
container, closure, or the affected infant formula for use.
    (2) Any ingredient, container, or closure that has been reprocessed
or otherwise reconditioned shall be the subject of a documented review
and

material disposition decision by an individual qualified by education,
training, or experience to determine whether it may be released for
use.
    (3) A manufacturer shall not reprocess or otherwise recondition an
ingredient, container, or closure rejected because it is contaminated
with microorganisms of public health significance or other
contaminants, such as heavy metals.
    (f) If an ingredient, container, or closure that complies with a
manufacturer's specifications, or that has been released for use
following a material review and disposition decision, is subsequently
exposed to air, heat, or other conditions that may adversely affect it,
or if a manufacturer reasonably believes that an ingredient, container,
or closure that complies with a manufacturer's specifications, or that
has been released for use following a material review and disposition
decision, has been exposed to air, heat, or other conditions that may
adversely affect it, the ingredient, container, or closure shall be
quarantined under a system designed to prevent its use in the
manufacture of infant formula until an individual qualified by
education, training, or experience has conducted a documented review
and has made and documented a material disposition decision to reject
the ingredient, container, or closure; to reprocess or otherwise
recondition the ingredient, container, or closure; or to approve and
release the ingredient, container, or closure for use.
    (1) Any ingredient, container, or closure that is reprocessed or
otherwise reconditioned shall be retested or reexamined and be the
subject of a documented review and material disposition decision by an
individual qualified by education, training, or experience to determine
whether the ingredient, container, or closure should be rejected,
further reprocessed or otherwise further reconditioned, or approved and
released for use.
    (2) Any rejected ingredient, container, or closure shall be clearly
identified as having been rejected for use in infant formula
manufacturing or processing operations and shall be controlled under a
quarantine system designed to prevent its use in infant formula
manufacturing or processing operations.
    (3) Any ingredient, container, or closure that has not been
manufactured, packaged, labeled, or held under conditions to prevent
adulteration under section 402(a)(1) through (a)(4) of the Federal
Food, Drug, and Cosmetic Act (21 U.S.C. 342(a)(1) through (a)(4)) shall
not be approved and released for use.
    (g) A manufacturer shall make and retain records, in accordance
with Sec.  106.100(f)(6), on the ingredients, containers, and closures
used in the manufacture of infant formula.

Sec.  106.50  Controls to prevent adulteration during manufacturing.

    (a) A manufacturer shall prepare and follow a written master
manufacturing order that establishes controls and procedures for the
production of an infant formula.
    (1) The manufacturer shall make and retain records, in accordance
with Sec.  106.100(e), that include complete information relating to
the production and control of the production aggregate. An individual
qualified by education, training, or experience shall conduct an
investigation of any deviations from the master manufacturing order and
document any corrective action taken.
    (2) Changes made to the master manufacturing order shall be
drafted, reviewed, and approved by a responsible official and include
an evaluation of the effect of the change on the nutrient content and
the suitability of the formula for infants.
    (b) A manufacturer shall establish controls to ensure that each raw
or in-process ingredient required by the master manufacturing order is
examined by one person and checked by a second person or system. This
checking shall ensure that the correct ingredient is added during the
manufacturing process, that the ingredient has been released for use in
infant formula, and that the correct weight or measure of the
ingredient is added to the production unit.
    (c) A manufacturer shall establish a system of identification for
the contents of all compounding and storage containers, processing
lines, and major equipment used during the manufacture of a production
aggregate of an infant formula. The system shall permit the
identification of the processing stage and the unique identification
number for the particular production unit or production aggregate of
infant formula.
    (d) A manufacturer shall establish controls to ensure that the
nutrient levels required by Sec.  107.100 of this chapter are
maintained in the formula, and that the formula is not contaminated
with microorganisms or other contaminants. Such controls shall include:
    (1) The mixing time; the speed, temperature, and flow rate of
product; and other critical parameters necessary to ensure the addition
of required ingredients to, and the homogeneity of, the formula;
    (2) The spray-drying process for powdered infant formula, including
the filtering of the intake air before heating, to prevent microbial
and other contamination;
    (3) The removal of air from the finished product to ensure that
nutrient deterioration does not occur;
    (4) Ensuring that each container of finished product is properly
sealed. Such controls shall involve use of established procedures,
specifications, and intervals of examination that are designed by
qualified individuals and are sufficient to:
    (i) Detect visible closure or seal defects, and
    (ii) Determine closure strength through destructive testing. A
manufacturer of a liquid infant formula that is a thermally processed
low-acid food packaged in a hermetically sealed container shall perform
such closure integrity testing in accordance with Sec.  113.60(a) of
this chapter.
    (e) A manufacturer shall establish controls that ensure that the
equipment used at points where control is deemed necessary to prevent
adulteration is monitored, so that personnel will be alerted to
malfunctions.
    (f) A manufacturer shall establish controls for in-process material
as follows:
    (1) For any specification established in accordance with Sec.
106.6(c)(1) that a manufacturer fails to meet for in-process material,
an individual qualified by education, training, or experience shall
conduct a documented review and shall make a material disposition
decision to reject the affected in-process material, to reprocess or
otherwise recondition the affected in-process material, or to approve
and release the affected in-process material for use or distribution;
    (2) Pending a documented review and material disposition decision,
any in-process material that fails to meet any specification
established in accordance with Sec.  106.6(c)(1) shall be clearly
identified as such and shall be controlled under a quarantine system
designed to prevent its use in manufacturing or processing operations
until completion of the documented review and material disposition
decision;
    (3) Any in-process material that has been reprocessed or otherwise
reconditioned shall be the subject of a documented review and material
disposition decision by an individual qualified by education, training,
or experience to determine whether it may be released for use; and
    (4) Any rejected in-process material shall be clearly identified as
having been rejected for use in infant formula

and shall be controlled under a quarantine system designed to prevent
its use in infant formula manufacturing or processing operations.

Sec.  106.55  Controls to prevent adulteration from microorganisms.

    (a) A manufacturer of infant formula shall establish a system of
process controls covering all stages of processing that is designed to
ensure that infant formula does not become adulterated due to the
presence of microorganisms in the formula or in the processing
environment.
    (b) A manufacturer of liquid infant formula shall comply, as
appropriate, with the procedures specified in part 113 of this chapter
for thermally processed low-acid foods packaged in hermetically sealed
containers and part 114 of this chapter for acidified foods.
    (c) A manufacturer of powdered infant formula shall test
representative samples of each production aggregate of powdered infant
formula at the final product stage, before distribution, to ensure that
each production aggregate meets the microbiological quality standards
in the table in paragraph (e) of this section.
    (d) A manufacturer shall make and retain records, in accordance
with Sec.  106.100(e)(5)(ii) and (f)(7), on the testing of infant
formulas for microorganisms.
    (e) A powdered infant formula that contains any microorganism that
exceeds the M value listed for that microorganism in the table in
paragraph (e) of this section shall be deemed adulterated under
sections 402(a)(1), 402(a)(4), and 412(a)(3) of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 350a(a)(3)). The Food and Drug
Administration will determine compliance with the M values listed below
using the latest edition of the Bacteriological Analytical Manual (BAM)
(http://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/BacteriologicalAnalyticalManualBAM/default.htm) (accessed April 8,
2013).

----------------------------------------------------------------------------------------------------------------
                 Microorganism                       n \1\                 Sample size                M value
----------------------------------------------------------------------------------------------------------------
Cronobacter spp...............................              30  10 g (grams)....................          \2\ 0.
Salmonella spp................................              60  25 g............................          \2\ 0.
----------------------------------------------------------------------------------------------------------------
\1\ Number of samples.
\2\ None detected.

Sec.  106.60  Controls to prevent adulteration during packaging and
labeling of infant formula.

    (a) A manufacturer shall examine packaged and labeled infant
formula during finishing operations to ensure that all containers and
packages in the production aggregate have the correct label, the
correct use-by date, and the correct code established under Sec.
106.80.
    (b) Labels shall be designed, printed, and applied so that the
labels remain legible and attached during the conditions of processing,
storage, handling, distribution, and use.
    (c) Packaging used to hold multiple containers of an infant formula
product shall be labeled as follows:
    (1) Where all containers are the same infant formula product and
all bear the same code established under Sec.  106.80, the packaging
label shall include the product name, the name of the manufacturer,
distributor, or shipper, and the code established under Sec.  106.80.
    (2) Where the containers are not the same infant formula product or
do not all bear the same code established under Sec.  106.80, the
packaging label shall:
    (i) Include the product name of each product, the name of the
manufacturer, distributor, or shipper of each product, the code
established under Sec.  106.80 for each product, and a ``use by'' date
that is no later than the ``use by'' date of the container exhibiting
the closest ``use by'' date applied to satisfy the requirement of Sec.
107.20(c) of this chapter; or
    (ii) Include a unique identification number assigned by the
packager, provided that the distributor of the package maintains a
record linked to such unique number that identifies the product name of
each product, the name of the manufacturer, distributor, or shipper of
each product, the code established under Sec.  106.80 for each product,
and the ``use by'' date for each product applied to satisfy the
requirement of Sec.  107.20(c) of this chapter.

Sec.  106.70  Controls on the release of finished infant formula.

    (a) A manufacturer shall control under a quarantine system designed
to prevent use or distribution of each production aggregate of infant
formula until it determines that the production aggregate meets all of
the manufacturer's specifications, including those adopted to meet the
standards of Sec.  106.55 on microbiological contamination and of Sec.
106.91(a) on quality control procedures, or until the documented review
of the failure to meet any of the manufacturer's specifications finds
that the failure does not result in, or could not lead to, adulteration
of the product.
    (b) Any production aggregate of infant formula that fails to meet
any of the manufacturer's specifications shall be quarantined under a
system designed to prevent its use in the manufacture of infant formula
or its distribution until an individual qualified by education,
training, or experience has conducted a documented review and has made
and documented a material disposition decision to reject the infant
formula; to reprocess or otherwise recondition the infant formula; or
to approve and release the infant formula. Any production aggregate of
infant formula that is reprocessed or otherwise reconditioned shall be
the subject of a documented review and material disposition decision by
an individual qualified by education, training, or experience to
determine whether it may be released for use or distribution.
    (c) Any rejected infant formula shall be clearly identified as
having been rejected for use and shall be controlled under a quarantine
system designed to prevent its release or distribution.
    (d) A production aggregate of infant formula, including a
reprocessed or reconditioned production aggregate, that does not meet
the nutrient requirements of section 412(i) of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 350a(i)) or that has not been manufactured,
packaged, labeled, and held under conditions to prevent adulteration
under sections 402(a)(1) through (a)(4) of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 342(a)(1) through (a)(4)) shall not be approved
and released for distribution.

Sec.  106.80  Traceability.

    Each production aggregate of infant formula shall be coded with a
sequential number that identifies the product and the establishment
where the product was packed and that permits tracing of all stages of
manufacture of that production aggregate, including the year, the days
of the year, and the period during those days that the product was
packed, and the receipt and handling of raw materials used.

Sec.  106.90  Audits of current good manufacturing practice.

    (a) A manufacturer of an infant formula, or an agent of such
manufacturer, shall conduct regularly scheduled audits to determine
whether the manufacturer has complied with the current good
manufacturing practice regulations in this subpart. Such audits shall
be conducted at a frequency that is required to ensure compliance with
such regulations.
    (b) The audits required by paragraph (a) of this section shall be
performed by an individual or a team of individuals who, as a result of
education, training, or experience, is knowledgeable in all aspects of
infant formula production and of the Agency's regulations concerning
current good manufacturing practice that such individual or team is
responsible for auditing. This individual or team of individuals shall
have no direct responsibility for the matters that such individual or
team is auditing and shall have no direct interest in the outcome of
the audit.

Subpart C--Quality Control Procedures

Sec.  106.91  General quality control.

    (a) During manufacture, a manufacturer shall test each production
aggregate for nutrients as follows:
    (1) Each nutrient premix used in the manufacture of an infant
formula shall be tested for each nutrient (required under Sec.  107.100
of this chapter or otherwise added by the manufacturer) that the
manufacturer is relying on the premix to provide, to ensure that the
premix is in compliance with the manufacturer's specifications;
    (2) During the manufacturing process, after the addition of the
premix, or at the final product stage but before distribution, each
production aggregate of infant formula shall be tested for at least one
indicator nutrient for each of the nutrient premixes used in the infant
formula to confirm that the nutrients supplied by each of the premixes
are present, in the proper concentration, in the production aggregate
of infant formula.
    (3) At the final product stage, before distribution of an infant
formula, each production aggregate shall be tested for vitamins A, C,
E, and thiamin.
    (4) During the manufacturing process or at the final product stage,
before distribution, each production aggregate shall be tested for all
nutrients required to be included in such formula under Sec.  107.100
of this chapter for which testing is not conducted for compliance with
paragraphs (a)(1) or (a)(3) of this section and for any nutrient added
by the manufacturer for which testing is not conducted for compliance
with paragraph (a)(1) of this section.
    (b) A manufacturer shall test each production aggregate of finished
product for nutrients as follows:
    (1) For an infant formula that is a new infant formula, Sec.
106.3, the manufacturer shall collect, from each manufacturing site and
at the final product stage, a representative sample of the first
production aggregate of packaged, finished formula in each physical
form (powder, ready-to-feed, or concentrate) and evaluate the levels of
all nutrients required under Sec.  107.100 of this chapter and all
other nutrients added by the manufacturer. The manufacturer shall
repeat such testing every 3 months thereafter throughout the shelf-life
of the product.
    (2) The manufacturer shall collect, from each manufacturing site
and at the final product stage, a representative sample of each
subsequent production aggregate of packaged, finished formula in each
physical form (powder, ready-to-feed, or concentrate) and evaluate the
levels of all nutrients required under Sec.  107.100 and all other
nutrients added by the manufacturer. The manufacturer shall repeat such
testing at the midpoint and at the end of the shelf-life of the
product.
    (3) If the results of the testing required by paragraph (b)(1) of
this section do not substantiate the shelf life of the infant formula,
the manufacturer shall either repeat the testing required by such
paragraph on a subsequently produced production aggregate to
substantiate the shelf life of the infant formula or revise the shelf
life label statement for such product so that such statement is
substantiated by the stability testing results.
    (4) If results of the testing required by paragraph (b)(2) of this
section show that any required nutrient is not present in the
production aggregate of infant formula at the level required by Sec.
107.100 of this chapter or that any nutrient added by the manufacturer
is not present at the level declared on the label of the production
aggregate of infant formula, the manufacturer shall:
    (i) Investigate the cause of such variance in the level of any
required or added nutrient;
    (ii) Evaluate the significance, if any, of the results for other
production aggregates of the same formula that have been released for
distribution;
    (iii) Address, as appropriate, all production aggregates of formula
released for distribution that are implicated by the testing results;
and
    (iv) Determine whether it is necessary to repeat the testing
required by paragraph (b)(1) of this section.
    (5) The testing required by paragraphs (b)(1) and (b)(2) of this
section is not required to evaluate the level of minerals present in
the infant formula.
    (c) All quality control testing shall be conducted using
appropriate, scientifically valid test methods.
    (d) A manufacturer shall make and retain quality control records in
accordance with Sec.  106.100(e)(5)(i).

Sec.  106.92  Audits of quality control procedures.

    (a) A manufacturer of an infant formula, or an agent of such a
manufacturer, shall conduct regularly scheduled audits to determine
whether the manufacturer has complied with the requirements for quality
control procedures that are necessary to ensure that an infant formula
provides nutrients in accordance with section 412(b) and (i) of the
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 350a(b) and (i)) and is
manufactured in a manner designed to prevent adulteration of the infant
formula under section 412(a)(1) and (a)(3) of the Federal Food, Drug,
and Cosmetic Act. Such audits shall be conducted at a frequency that is
required to ensure compliance with the requirements for quality control
procedures.
    (b) The audits required by paragraph (a) of this section shall be
performed by an individual or a team of individuals who, as a result of
education, training, or experience, is knowledgeable in all aspects of
infant formula production and of the regulations concerning quality
control procedures that such individual or team is responsible for
auditing. This individual or team of individuals shall have no direct
responsibility for the matters that such individual or team is auditing
and shall have no direct interest in the outcome of the audit.

Subpart D--Conduct of Audits

Sec.  106.94  Audit plans and procedures.

    (a) A manufacturer shall develop and follow a written audit plan
that is available at the manufacturing facility for Food and Drug
Administration inspection.
    (b) The audit plan shall include audit procedures that set out the
methods the manufacturer uses to determine whether the facility is
operating in accordance with current good manufacturing practice, with
the quality control procedures that are necessary to ensure that an
infant formula provides nutrients in accordance with sections

412(b) and (i) of the Federal Food, Drug, and Cosmetic Act, and in a
manner designed to prevent adulteration of the infant formula.
    (c) The audit procedures shall include:
    (1) An evaluation of the production and in-process control system
established under Sec.  106.6(b) by:
    (i) Observing the production of infant formula and comparing the
observed process to the written production and in-process control plan
required under Sec.  106.6(b);
    (ii) Reviewing records of the monitoring of points, steps, or
stages where control is deemed necessary to prevent adulteration; and
    (iii) Reviewing records of how deviations from any specification at
points, steps, or stages where control is deemed necessary to prevent
adulteration were handled; and
    (2) A review of a representative sample of all records maintained
in accordance with Sec.  106.100(e) and (f).

Subpart E--Quality Factors for Infant Formulas

Sec.  106.96  Requirements for quality factors for infant formulas.

    The regulations set forth in this subpart define the minimum
requirements for quality factors for infant formulas:
    (a) An infant formula shall meet the quality factor of normal
physical growth.
    (b) A manufacturer of an infant formula that is not an eligible
infant formula shall demonstrate that a formula supports normal
physical growth in infants when fed as a sole source of nutrition by
conducting, in accordance with good clinical practice, an adequate and
well-controlled growth monitoring study of the infant formula that:
    (1) Is no less than 15 weeks in duration, enrolling infants no more
than 2 weeks old at time of entry into the study;
    (2) Includes the collection and maintenance of data on formula
intake and anthropometric measures of physical growth, including body
weight, recumbent length, head circumference, average daily weight
increment, and average daily recumbent length increment;
    (3) Includes anthropometric measurements made at the beginning and
end of the study, and at least four additional measurements made at
intermediate time points with three of the six total measurements made
within the first 4 weeks of the study and three measurements made at
approximately 4-week intervals over the remaining 11 weeks of the
study;
    (4) Compares the anthropometric data for the test group to a
concurrent control group or groups at each time point and compares the
anthropometric data for each infant (body weight for age, body length
for age, head circumference for age, and weight for length) in the test
group and the control group to the 2009 CDC growth charts, which are
incorporated by reference at Sec.  106.160; and
    (5) Compares the data on formula intake of the test group with a
concurrent control group or groups and a scientifically appropriate
reference.
    (c) The Food and Drug Administration will exempt a manufacturer
from the requirements of paragraph (b) of this section, if:
    (1) The manufacturer requests an exemption and provides assurances,
as required under Sec.  106.121, that the changes made by the
manufacturer to an existing infant formula are limited to changing the
type of packaging of an existing infant formula (e.g., changing from
metal cans to plastic pouches); or
    (2) The manufacturer requests an exemption and provides assurances,
as required under Sec.  106.121, which demonstrate that:
    (i) An alternative method or study design that is based on sound
scientific principles is available to show that the formula supports
normal physical growth in infants when the formula is fed as the sole
source of nutrition;
    (ii) The change made by the manufacturer to an existing formula
does not affect the bioavailability of the formula, including the
bioavailability of nutrients in such formula; or
    (iii) The manufacturer markets a formulation in more than one form
(e.g., liquid and powdered forms) and the quality factor requirements
are met by the form of the formula that is processed using the method
that has the greatest potential for adversely affecting nutrient
content and bioavailability.
    (d) A manufacturer of a new infant formula that is not an eligible
infant formula shall, in accordance with Sec.  106.100(p)(1), make and
retain records demonstrating that the formula meets the quality factor
of normal physical growth.
    (e) An infant formula shall meet the quality factor of sufficient
biological quality of protein.
    (f) A manufacturer of an infant formula that is not an eligible
infant formula shall demonstrate that a formula meets the quality
factor of sufficient biological quality of protein by establishing the
biological quality of the protein in the infant formula when fed as the
sole source of nutrition using an appropriate modification of the
Protein Efficiency Ratio (PER) rat bioassay described in the ``Official
Methods of Analysis of AOAC International,'' 18th ed., sections 45.3.04
and 45.3.05, ``AOAC Official Method 960.48 Protein Efficiency Ratio Rat
Bioassay,'' which is incorporated by reference at Sec.  106.160. The
PER rat bioassay shall be conducted on a formula and the results
evaluated prior to the initiation of a growth monitoring study of the
formula that is required under paragraph (b) of this section.
    (g) The Food and Drug Administration will exempt a manufacturer
from the requirements of paragraph (f) of this section, if:
    (1) The manufacturer requests an exemption and provides assurances
as required under Sec.  106.121 that the changes made by the
manufacturer to an existing infant formula are limited to changing the
type of packaging of an existing infant formula (e.g., changing from
metal cans to plastic pouches); or
    (2) The manufacturer requests an exemption and provides assurances,
as required under Sec.  106.121, that demonstrate that the change made
by the manufacturer to an existing formula does not affect the
bioavailability of the protein.
    (h) A manufacturer of a new infant formula that is not an eligible
infant formula shall, in accordance with Sec.  106.100(q), make and
retain records demonstrating that the formula meets the quality factor
of sufficient biological quality of protein.
    (i) The following provisions for requirements for quality factors
apply only to an ``eligible infant formula'' as defined in Sec.  106.3:
    (1) An eligible infant formula that fulfills one or more of the
following criteria meets the quality factor of normal physical growth:
    (i) The scientific evidence on such infant formula meets the
requirements of paragraph (b) of this section that apply to infant
formula that is not an eligible infant formula;
    (ii) The scientific evidence on such infant formula meets the
following provisions:
    (A) The evidence is an adequate and well-controlled growth study,
conducted in accordance with good clinical practice, to determine
whether an infant formula supports normal physical growth in infants
when the formula is fed as the sole source of nutrition;
    (B) The growth study is no less than 4 months in duration,
enrolling infants no more than 1 month old at time of entry into the
study;

    (C) The growth study collects from the study subjects data on
anthropometric measures of physical growth, including body weight,
recumbent length, head circumference, and average daily weight
increment, and plots the data on the following charts from ``Physical
Growth: National Center for Health Statistics Percentiles'' for body
weight, body length, and head circumference, which are incorporated by
reference at Sec.  106.160:
    (1) Figure 1. Length by age percentiles for girls aged birth-36
months (p. 609);
    (2) Figure 2. Length by age percentiles for boys aged birth-36
months (p. 610);
    (3) Figure 3. Weight by age percentiles for girls aged birth-36
months (p. 611);
    (4) Figure 4. Weight by age percentiles for boys aged birth-36
months (p. 612);