**[ATTACHMENT B]{.underline}**

# FDA Infant Formula GMP Regulation

**(Redlined against IFC Suggested Edits**[^1]**)**

Part 106 INFANT FORMULA REQUIREMENTS PERTAINING TO CURRENT GOOD
MANUFACTURING PRACTICE, QUALITY CONTROL PROCEDURES, QUALITY FACTORS,
RECORDS AND REPORTS, AND NOTIFICATION

106.1 Status and applicability of the regulations in part 106.

106.1(a) The criteria set forth in subparts B, C, and D of this part
prescribe the steps that manufacturers must take under section 412(b)(2)
and (b)(3) of the Federal Food, Drug, and Cosmetic Act (the act) 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
act.

106.1(b) The criteria set forth in subpart E of this part prescribe the
quality factor requirements that infant formula must meet under section
412(b)(1) of the 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 act.

106.1(c) The criteria set forth in subpart F of this part implement the
record retention requirements established in section 412(b)(4) of the
act. Failure to comply with any regulation in subpart F of this part is
a violation of section 301(e) of the act.

106.1(d) The criteria set forth in subpart G of this part describe the
circumstances in which infant formula manufacturers are required to
register with, submit to, or notify the Food and Drug Administration,
and the content of those registrations, submissions, or notifications,
under section 412(c), (d), and (e) of the act. Failure to comply with
any regulation in subpart G of this part is a violation of section
301(s) of the act.

106.3 Definitions.

106.3(a) Batch means a specific quantity of an infant formula ~~or other
material~~ that is intended to have uniform [composition]{.mark},
character and quality, ~~within specified limits~~, and is produced
according to a [master]{.mark} ~~single~~ manufacturing order during the
same cycle of manufacture.

106.3(b) 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.

106.3(c) 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.

106.3(d) Infant means a person not more than 12 months of age.

106.3(e) 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.

106.3(f) In-process batch means a combination of ingredients at any
point in the manufacturing process before packaging.

106.3(g) Lot means a batch, ~~or~~ a specifically identified portion of
a batch, [or other material]{.mark} having uniform [composition]{.mark},
character and quality ~~within specified limits~~; or, in the case of an
infant formula produced by continuous process, it is a specific
identified amount produced in a unit of time or quantity in a manner
that assures its having uniform [composition]{.mark}, character and
quality ~~within specified limits~~.

106.3(h) Lot number, control number, or batch 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 batch or lot of infant formula
or other material can be determined.

106.3(i) 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:

106.3(i)(1) Any infant formula produced by a manufacturer who is
entering the U.S. market;

106.3(i)(2) Any infant formula powder processed and introduced for
commercial or charitable distribution by a manufacturer who previously
only produced liquids (or vice versa);

106.3(i)(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;

106.3(i)(4) Any infant formula manufactured on a new processing line or
in a new plant;

106.3(i)(5) Any infant formula manufactured containing a new
[nutrient]{.mark} ~~constituent~~ not listed in section 412(i) of the
act, such as taurine or L-carnitine;

106.3(i)(6) Any infant formula processed by a manufacturer on new
equipment that utilizes a new technology or principle (e.g., a change
from terminal sterilization to aseptic processing); and

106.3(i)(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).

[106.3(j) Minor change in an infant formula means any new formulation,
or any change of ingredients or processes where experience or theory
would not predict a possible significant adverse impact on nutrient
levels or nutrient availability. Minor changes may or may not affect
whether a formula is adulterated under section 412(a) of the Act;
changes that affect whether a formula is adulterated under section
412(a) of the Act would require the manufacturer to notify FDA prior to
first processing.]{.mark}

[106.3(j)(1) Examples of minor changes to infant formulas
include:]{.mark}

[]{.mark}

[106.3(j)(1)(i) Reduction of a nutrient that results in a label change,
change in a nutrient level which is within 10% of the nutrient levels,
minimum or maximum required by Section 412(g) of the FFDCA and is at
least 10% closer to the required level;]{.mark}

[106.3(j)(1)(ii) Any change in the identity of the ingredients providing
nutrients required under section 412 (g) of the Act or trace nutrients
added voluntarily consistent with 21 CFR 107.10(b)(5);]{.mark}

[]{.mark}

[106.3(j)(1)(iii) Any design change in the formulation or processing of
an infant formula which the manufacturer determines calls for
non-routine nutrient testing prior to release, for the purpose of
determining whether a possible change has occurred in the levels of
nutrients in meeting requirements of Section 412(g) of the Act.]{.mark}

[]{.mark}

[106.3(j)(2) Examples of minor changes to infant formulas that do not
require notification prior to first processing include:]{.mark}

[]{.mark}

[106.3(j)(2)(i) Minor reduction of iron level;]{.mark}

[]{.mark}

[106.3(j)(2)(ii) Replacing certain nutrient forms with another
form;]{.mark}

[]{.mark}

[106.3(j)(2)(iii) Adjustments in the quantity of a nutrient in a premix
or individually added nutrient that results in a specification change
for that nutrient in the finished product;]{.mark}

[]{.mark}

[106.3(j)(2)(iv) Changes in time-temperature conditions of preheating
during handling of bulk product that cannot reasonably be expected to
cause an adverse impact on nutrient levels or nutrient
availability;]{.mark}

[]{.mark}

[106.3(j)(2)(v) Changes in oxygen content of a packaged product that
might have a minimal effect on the level of nutrients.]{.mark}

106.3(~~j~~[k]{.mark}) 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.

~~106.3(k) Microorganisms means yeasts, molds, bacteria, and viruses and
includes, but is not limited to, species having public health
significance.~~

106.3(l) New infant formula means:

\(1\) An infant formula manufactured by a person that has not previously
manufactured an infant formula for the U.S. market, 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.

106.3(m) [Required]{.mark} ~~N~~nutrient means any vitamin, mineral, or
other substance or ingredient [in infant formula]{.mark} that is
required ~~in accordance with the table set out in section 412(i)(1)
of~~ by the 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 National Research Council through its development of a
Recommended Dietary Allowance or an Estimated Safe and Adequate Daily
Dietary Intake range, or that has been identified as essential for
infants by the Food and Drug Administration through a Federal Register
publication~~ [pursuant to the act]{.mark}.

106.3(n) Nutrient premix means a combination of ingredients containing
two or more nutrients received from a supplier or prepared by an infant
formula manufacturer.

106.3(o) Quality factors mean those factors necessary to demonstrate
[the bioavailability of a nutrient and the maintenance of level or
potency of nutrients through an expected shelf life of the
product]{.mark} ~~that the infant formula, as prepared for market,
provides nutrients in a form that is bioavailable and safe as shown by
evidence that demonstrates that the formula supports healthy growth when
fed as a sole source of nutrition~~.

106.3(p) 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.

106.3(q) Shall is used to state mandatory requirements.

106.3(r) Should is used to state recommended or advisory procedures or
to identify recommended equipment.

[106.3(s) Responsible party means the manufacturer of an infant formula
when all manufacturing steps are performed by a single entity; however,
when several entities are involved in the manufacture of a given
formula, it means the manufacturer or other entity that has agreed to
assume responsibility for ensuring that all requirements for
notification and/or assurance under these regulations are
satisfied.]{.mark}

[106.3(t) Specifications means quality control limits or standards for
raw materials, in-process materials and finished product, which are
established by the manufacturer for purposes of controlling quality and
consistency for infant formula. Failure to meet an established
specification requires a documented review and material disposition
decision.]{.mark}

[106.3(u) Target Value means quality control limits or standards for raw
materials, in-process materials and finished product which are
established by the manufacturer for purposes of targeting the
manufacturing process to a tight range within broader specifications.
Failure to meet an established target value shall result in an immediate
review and adjustment, if necessary, during the manufacturing process.
No documented review and material disposition is needed when a target
value is not met, as long as the established specification is
met.]{.mark}

[106.3(v) Critical is used to describe systems or equipment that have
been designated by the infant formula manufacturer as necessary to
control in order to prevent adulteration.]{.mark}

**Subpart B\--Current Good Manufacturing Practice**

**106.5 Current good manufacturing practice.**

106.5(a) The regulations set forth in this subpart and, for liquid
infant formulas, in part 113 of this chapter 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.

106.5(b) The failure to comply with any regulation set forth in this
subpart or, for liquid infant formulas, in part 113 of this chapter 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 (the act).

106.6 Production and in-process control system.

106.6(a) Manufacturers 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~~
[those]{.mark} stages of processing, [storage and distribution that are
under the manufacturer\'s control]{.mark}, from the receipt and
acceptance of the raw materials, ingredients, and components through the
storage and distribution of the finished product[,]{.mark} and shall be
designed to ensure that all the requirements of this subpart are met.

106.6(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.

106.6(c) ~~At any point, step, or stage~~ [The manufacturer shall
identify the points, steps, or stages]{.mark} in the production process
where control is ~~necessary~~ [critical]{.mark} to prevent
adulteration~~, the~~[. The]{.mark} manufacturer shall[, with respect to
such points]{.mark}:

106.6(c)(1) Establish ~~standards or~~ specifications [and, where
appropriate, target values]{.mark} ~~to be met~~;

106.6(c)(2) Monitor the production and in-process control point, step,
or stage;

106.6(c)(3) Establish ~~corrective action plans for use when a standard
or~~ [standard operating procedures to address when a]{.mark}
specification established in accordance with paragraph ~~(b)(1)~~
[(c)(1)]{.mark} of this section is not met;

106.6(c)(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~~ [whether]{.mark} deviations from ~~standards or~~
specifications that have been established in accordance with paragraph
(c)(1) of this section [have public health significance]{.mark}. This
review shall be conducted by an individual qualified by training and
experience to conduct such reviews; and

106.6(c)(5) Establish Record keeping procedures, in accordance with Sec.
106.100(e)(3), that ensure that compliance with the requirements of this
section is documented.

106.10 Controls to prevent adulteration by workers.

[Delete]{.mark}

[or]{.mark}

106.10(a) ~~There~~ [The manufacturer]{.mark} shall ~~be~~
[designate]{.mark} sufficient personnel, qualified by training and
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 they
are correctly and fully performed.

~~106.10(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, but is not limited to:~~

~~106.10(b)(1) Wearing clean outer garments and, as necessary,
protective apparel such as head, face, hands, and arm coverings; and~~

~~106.10(b)(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.~~

~~106.10(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.~~

**106.20 Controls to prevent adulteration caused by facilities.**

106.20(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.

106.20(b) ~~Separate areas shall be designated for holding~~ [A control
system shall be established by the manufacturer to control by status the
storage and use of]{.mark} raw materials, in‑processing materials, and
~~final product~~ [finished]{.mark} infant formula[. This system shall
include the differentiation of the following]{.mark}:

106.20(b)(1) Pending release for use in infant formula production or
pending release of the final product,

106.20(b)(2) After rejection for use in [or as]{.mark} infant formula
~~and before disposition~~, and

106.20(b)(3) After release for use in [or as]{.mark} infant formula
production or after release of the final product.

~~106.20(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.~~

~~106.20(d) Air filtration systems, including prefilters and particulate
matter air filters, shall be used on air supplies to production areas
where ingredients or infant formula are directly exposed to the
atmosphere.~~

~~106.20(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.~~

106.20(~~f~~[c]{.mark})(1) 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 set
forth in 40 CFR part 141, except that ~~the fluoride level of the water
used in infant formula manufacturing shall be as low as possible~~
[fluoride removal systems shall be employed for fluoridated water
supplies]{.mark}. The water shall be supplied under continuous positive
pressure in a plumbing system that is free of defects that could
contaminate an infant formula.

106.20(~~f~~[c]{.mark})(2) Manufacturers 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.

106.20(~~f~~[c]{.mark})(3) Manufacturers 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.

106.20(~~f~~[c]{.mark})(4) Manufacturers shall make and retain records,
in accordance with §106.100(f)(1), of the frequency and results of
testing of the water used in the production of infant formula.

~~106.20(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.~~

~~106.20(h) When steam comes in direct contact with infant formula, it
shall be safe and free of rust and other particulate matter that may
contaminate the formula. Boiler water additives in the steam shall be
used in accordance with 173.310 of this chapter.~~

~~106.20(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, and
single‑service towels and that are maintained in good repair and in a
sanitary condition at all times, and that these facilities 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.~~

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

106.30(a) Equipment used in the manufacture, processing, packing or
holding of an infant formula shall be of appropriate design and shall be
installed to facilitate its intended function and its cleaning and
maintenance.

~~106.30(b) Equipment and utensils used in the manufacture, processing,
packing, or holding of an infant formula shall be constructed so that
surfaces that contact ingredients, in‑process materials, or infant
formula are made of nontoxic materials and are not reactive or
absorptive. Such equipment and utensils shall be designed to be easily
cleanable and to withstand the environment of their intended use. All
surfaces that contact ingredients, in‑process materials, or infant
formula shall be cleaned, sanitized, and maintained to protect infant
formula from being contaminated by any source. Sanitizing agents used on
food‑contact surfaces must comply with 178.1010 of this chapter.~~

106.30(~~c~~[b]{.mark}) Manufacturers shall ensure that substances, such
as lubricants or coolants, that are required for operation of infant
formula manufacturing equipment, but that would render the infant
formula adulterated if they contaminated the formula, do not come in
contact with formula ingredients, containers~~,~~ [and]{.mark}
closures~~, or in‑~~ [(prior to the closing/sealing operation),]{.mark}
or in-process materials or with infant formula itself [in a manner not
permitted by applicable food additive regulations]{.mark}.

106.30(~~d~~[c]{.mark})(1) Manufacturers shall ensure that instruments
used for measuring, regulating, or controlling mixing time and speed,
temperature, pressure, moisture, water activity, or other parameters at
points where control is deemed ~~necessary~~ [critical by the infant
formula manufacturer]{.mark} to prevent adulteration in the processing
of an infant formula are accurate, easily read, properly maintained, and
present in sufficient number for their intended use. The instruments and
controls shall be tested for accuracy (calibrated) against a known
reference standard [on or]{.mark} 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 [by the infant
formula manufacturer]{.mark} to ensure the accuracy of the instrument.
The known reference standard shall be certified for accuracy at routine
intervals specified in writing by the manufacturer of the instrument, or
as otherwise deemed necessary [by the infant formula
manufacturer]{.mark} to ensure the accuracy of the instrument.
Manufacturers shall make and retain records of the accuracy checks in
accordance with Sec. 106.100(f)(2).

106.30(~~d~~[c]{.mark})(2) Instruments and controls that cannot be
adjusted to agree with the reference standard shall be repaired or
replaced.

106.30(~~d~~[c]{.mark})(3) If calibration of an instrument (testing for
accuracy against a known reference standard) shows that a specification
or standard for a point where control is deemed necessary to prevent
adulteration has not been met, 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 §106.100(f)(2).

106.30(~~e~~[d]{.mark})(1) The temperature in cold storage compartments
that are used to store raw materials, in‑process materials, or final
product, and in thermal processing equipment used at points where
temperature control is necessary to prevent adulteration, shall be
monitored with such frequency as is necessary to ensure that temperature
control is maintained.

106.30(~~e~~[d]{.mark})(2) Cold storage compartments shall be maintained
at a temperature ~~of 40 deg. F (4.4 deg. C), or below~~ [confirmed by
the manufacturer to assure the quality and safety of in-process
materials.]{.mark}106.30(e)(3)(i) Cold storage compartments and thermal
processing equipment shall be equipped with easily readable, accurate
temperature-indicating devices.

106.30(~~e~~[d]{.mark})(3)(i) Cold storage compartments and thermal
processing equipment shall be equipped with easily readable, accurate
temperature‑indicating devices.

106.30(~~e~~[d]{.mark})(3)(ii) Thermal processing equipment shall ~~be
equipped with temperature‑recording devices that will reflect the true
temperature on a continuing basis. Cold~~ [meet the requirements of 21
C.F.R. Part 113. Temperature monitoring of cold]{.mark} storage
compartments shall be ~~equipped with either temperature‑recording
devices that will reflect the true temperature, on a continuing basis,
within the compartment or, in lieu of a temperature‑recording device, a
high temperature alarm or a maximum‑indicating thermometer that has been
verified to function properly. If the manufacturer uses either of the
latter options, it shall maintain a temperature log in which it notes
temperature with such frequency as is necessary to achieve~~ [of
sufficient frequency to assure proper]{.mark} control. Manufacturers
shall make and retain records, in accordance with Sec. 106.100(f)(3), of
the temperatures indicated or recorded by these devices.

~~106.30(e)(4) When a temperature‑recording device is used, such device
shall not read higher than the calibrated temperature‑indicating device
for thermal processing equipment or lower than the reference
temperature‑indicating device for cold storage compartments.~~

106.30(~~f~~[e]{.mark}) Equipment and utensils used in [an operating
production line for]{.mark} the manufacture of infant formula shall be
cleaned~~,~~ [and]{.mark} sanitized~~, and maintained~~ at regular
intervals [as determined by the manufacturer to be necessary]{.mark} to
prevent adulteration of the infant formula. An individual qualified by
training or experience to conduct such a review shall check all
cleaning~~,~~ [and]{.mark} sanitizing, ~~and maintenance~~ to ensure
that it has been satisfactorily completed. Manufacturers shall make and
retain records ~~on equipment cleaning, sanitizing, and maintenance,~~
in accordance with Sec. 106.100(f)(4).

~~106.30(g) 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 shall be treated in such a way
that their use will not contaminate the infant formula with unlawful
indirect food additives 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, the
manufacturer shall install a 0.5 micrometer or smaller filter as close
to the end of the gas line that feeds gas into the space, as
practical.~~

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

~~106.35(a)(1) For the purposes of this section, \"hardware\" means all
automatic equipment, including mechanical and electronic equipment
(including computers), that is used in production or quality control of
a infant formula.~~

~~106.35(a)(2) For the purposes of this section, \"software\" means any
programs, procedures, rules, and associated documentation used in the
operation of a system.~~

~~106.35(a)(3) For the purposes of this section, \"system\" means a
collection of components (including software and hardware) organized to
accomplish a specific function or set of functions in a specified
environment.~~

~~106.35(a)(4) For the purposes of this section, \"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.~~

[Delete]{.mark}

[or]{.mark}

106.35(~~b~~[a]{.mark})(1) All [critical]{.mark} 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.

[Delete]{.mark}

[or]{.mark}

106.35(~~b~~[a]{.mark})(2) The infant formula manufacturer shall ensure
that [critical]{.mark} hardware is routinely ~~calibrated,~~
inspected~~,~~ and checked according to written procedures.

[Delete]{.mark}

[or]{.mark}

106.35(~~b~~[a]{.mark})(3) The infant formula manufacturer shall check
and document the accuracy of input into, and output generated by, any
[critical]{.mark} system used in the production or quality control of an
infant formula. The degree and frequency of input/output verification
shall be based on the [manufacturer\'s assessment of the]{.mark}
complexity and reliability of the system and the level of risk
associated with the safe operation of the system. [Quality evaluations
should be used to substantiate the adequacy of the checks required by
this section.]{.mark}

[Delete]{.mark}

[or]{.mark}

106.35(~~b~~[a]{.mark})(4) The infant formula manufacturer shall ensure
that all [critical]{.mark} systems are ~~validated before their first
use to manufacture~~ [checked as per 106.35(b)(3) before the
release]{.mark} of commercial product [initially manufactured with these
systems]{.mark}.

[Delete]{.mark}

[or]{.mark}

106.35(~~b~~[a]{.mark})(5) The infant formula manufacturer shall ensure
that any [critical]{.mark} system that is modified is ~~revalidated~~
[reassessed]{.mark} after the modification and before ~~use of~~
[release of any infant formula manufactured with]{.mark} the modified
system ~~to manufacture commercial product~~. All modifications to
[critical]{.mark} 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.

[Delete]{.mark}

[or]{.mark}

106.35(~~c~~[b]{.mark}) The infant formula manufacturer shall make and
retain [necessary]{.mark} records, in accordance with Sec.
106.100(f)(5), concerning [critical]{.mark} automatic (mechanical or
electronic) equipment.

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

~~106.40(a) The only substances that may be used in infant formulas are
food ingredients whose use in infant formula is safe and suitable under
the applicable food safety provisions of the Federal Food, Drug, and
Cosmetic Act; that is, the substance is generally recognized as safe
(GRAS) for such use, is used in accordance with the agency\'s food
additive regulations, or is authorized by a prior sanction.~~

~~106.40(b) Infant formula containers and closures shall not be reactive
or absorptive so as to affect the safety of the infant formula, and all
packaging material that comes in contact with infant formula shall be
composed of substances that are GRAS for use in or on food, GRAS for
their intended use in food packaging, authorized by a prior sanction
issued by the agency, or authorized for use as an indirect food
additive. Any packaging material that comes in contact with infant
formula shall be used in accordance with any prescribed limitations.~~

106.40(~~c~~[a]{.mark}) Ingredients, containers, and closures used in
the manufacture of infant formula shall be identified with a batch or
lot number to be used in recording their disposition.

106.40(~~d~~[b]{.mark}) Infant formula manufacturers shall develop
written specifications for ~~their acceptance or rejection of~~
ingredients, containers, and closures used [as components]{.mark} in
infant formula manufacture~~. These specifications shall stipulate the
standards for acceptance or rejection of such ingredients, containers,
and closures as well as the procedures for determining whether the
ingredients, containers, and closures meet that standard. An individual
qualified by training or experience shall conduct an investigation of a
finding that any ingredients, containers, or closures used in a batch of
infant formula failed to meet any of the manufacturer\'s
specifications~~ [and packaging]{.mark}.

106.40(~~e~~[c]{.mark}) Ingredients, containers and closures shall be
~~stored in areas~~ [controlled by a system that]{.mark} clearly
~~designated for~~ [designates]{.mark}:

106.40(~~e~~[c]{.mark})(1) Materials pending release for use,

106.40(~~e~~[c]{.mark})(2) Materials released for use, or

106.40(~~e~~[c]{.mark})(3) Materials rejected for use in infant formula
production. Any lot of ingredients, containers, or closures that ~~does
not meet the manufacturer\'s specifications shall be rejected and~~ [has
been rejected shall be]{.mark} controlled under a quarantine system
designed to prevent its use in the manufacture of infant formula~~.~~[,
unless and until it is disposed of or reconditioned and found
acceptable.]{.mark}

106.40(~~f~~[d]{.mark}) If [the manufacturer determines that]{.mark} an
ingredient, a container, or a closure that has been tested and examined
is exposed to ~~air, heat, or other~~ conditions that ~~may~~ [could be
expected to]{.mark} adversely affect it, the ingredient, container, or
closure shall be retested or reexamined to ensure ~~that it still meets
the manufacturer\'s specifications.~~ [its acceptability for use in the
manufacturing process.]{.mark}

106.40(~~g~~[e]{.mark}) Manufacturers shall make and retain records, in
accordance with §106.100(f)(6), on the ingredients, containers, and
closures used in the manufacture of infant formula.

106.50 Controls to prevent adulteration during manufacturing.

106.50(a)(1) Manufacturers shall prepare and follow a written master
manufacturing order that establishes controls and procedures for the
production of an infant formula.

106.50(a)(2) The manufacturer shall make and retain records, in
accordance with §106.100(e), that include complete information relating
to the production and control of the batch. An individual qualified by
training or experience shall conduct an investigation of any deviations
from the master manufacturing order and any corrective actions taken.

106.50(a)(3) 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.

106.50(b) The 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 will 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 batch.

106.50(c) The manufacturer shall ~~identify the contents, including the
processing stage and the lot or batch number of a batch of infant
formula, of all compounding and storage containers, processing lines,
and major equipment~~ [establish a system that permits it to determine
the major equipment systems]{.mark} used during the production of a
batch of an infant formula.

106.50(d) The manufacturer shall establish [and document a system
of]{.mark} 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 but not be limited to:~~

~~106.50(d)(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;~~

~~106.50(d)(2) The spray‑drying process for powdered infant formula,
including the filtering of the intake air before heating, to prevent
microbial and other contamination;~~

~~106.50(d)(3) The removal of air from the finished product to ensure
that nutrient deterioration does not occur;~~

~~106.50(d)(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:~~

~~106.50(d)(4)(i) Detect visible closure or seal defects, and~~

~~106.50(d)(4)(ii) Determine closure strength through destructive
testing. Manufacturers of liquid infant formulas, which are thermally
processed low‑acid foods packaged in hermetically sealed containers,
shall perform such closure integrity testing in accordance with
113.60(a) of this chapter.~~

106.50(e) The 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.

106.50(f) The manufacturer shall establish controls that ensure that
rejected in-process materials:

106.50(f)(1) Are clearly identified as having been rejected for use in
an infant formula;

106.50(f)(2) Are controlled under a quarantine system designed to
prevent their use in manufacturing or processing operations for which
they are unsuitable;

[Delete]{.mark}

[or]{.mark}

106.50(f)(3) [If subjected to reprocessing,]{.mark} ~~M~~[m]{.mark}eet
the appropriate specifications~~, if reprocessed,~~ [or undergo a
documented material disposition decision]{.mark} before being released
for [further]{.mark} use in infant formula.

**106.55 Controls to prevent adulteration from microorganisms.**

106.55(a) Manufacturers of liquid infant formula shall comply with the
procedures specified in part 113 of this chapter for liquid infant
formula.

106.55(b) Manufacturers of powdered infant formula shall test
representative samples of every batch of the formula at the final
product stage, before distribution, to ensure that the infant formula
meets the microbiological quality standards listed in paragraph (c) of
this section.

106.55(c) Any powdered infant formula that contains any microorganism
that exceeds the M value listed for that microorganism in Table 1 of
this section will be deemed to be adulterated under sections 402 and 412
of the Federal Food, Drug, and Cosmetic Act (the act). FDA will
determine compliance with the M values listed below using the
Bacteriological Analytical Manual (BAM), 8th ed. (1995), published by
the AOAC International Association of Official Analytical Chemists,
which is incorporated by reference in accordance with 5 U.S.C. 552(a)
and 1 CFR part 51. Copies are available from the Association of Official
Analytical Chemists, 481 North Frederick Ave., Suite 500, Gaithersburg,
MD 20877, or may be examined at the Center for Food Safety and Applied
Nutrition\'s Library, 200 C St. SW, rm. 3321, Washington, DC, or may be
examined at the Office of the Federal Register, 800 North Capitol St.
NW, Suite 700, Washington, DC.

+--------------------------------------+-------------------------------+
| Microorganism                        | M Value[^1^]{.mark}           |
+--------------------------------------+-------------------------------+
| Aerobic Plate Count (APC)            | 10,000 CFU/gram (g).^2^       |
|                                      |                               |
| [Enterobacteriaceae (EB)]{.mark}^3^  | 3.0~~5~~ MPN/g.^4,5^          |
|                                      |                               |
| Fecal coliforms^6^                   | ~~3.05 MPN/g.~~               |
|                                      | [0.^7^]{.mark}                |
| *Salmonella*                         |                               |
|                                      | 0.^7^                         |
| *~~Listeria monocytogenes~~*         |                               |
|                                      | ~~0.^7\ ^~~                   |
| *Staphylococcus aureus*              |                               |
|                                      | 3.0~~5~~ MPN/g.               |
| *Bacillus cereus*^8^                 |                               |
|                                      | ~~100~~ [1000]{.mark} CFU/g.  |
+--------------------------------------+-------------------------------+
| ^1^ The M value is the maximum       |                               |
| allowable number of microorganisms   |                               |
| present in 1 g of dry infant         |                               |
| formula.                             |                               |
|                                      |                               |
| ^2^ CFU/g, colony forming units per  |                               |
| g. [Probiotic infant formulas are    |                               |
| exempted.]{.mark}                    |                               |
|                                      |                               |
| ^3^ M values for [EB]{.mark}         |                               |
| ~~coliforms~~ greater than [or equal |                               |
| to]{.mark} 3.0~~5~~ are not          |                               |
| violative if ~~testing for~~ fecal   |                               |
| coliforms [are not confirmed in the  |                               |
| EB test]{.mark} ~~results in an M    |                               |
| value equal to or less than 3.05~~.  |                               |
|                                      |                               |
| ^4^ MPN/g, most probable number per  |                               |
| g.                                   |                               |
|                                      |                               |
| ^5^ The MPN value of 3.0~~5~~ in     |                               |
| this table is derived from the       |                               |
| tables of calculated MPN values that |                               |
| appear in [the January 2001 revision |                               |
| of]{.mark} the 8th ed. of the BAM    |                               |
| when using an inoculation series of  |                               |
| 0.1, 0.01, and 0.001g (or ml) of the |                               |
| infant formula sample.               |                               |
|                                      |                               |
| ^6^ No [confirmation]{.mark} testing |                               |
| for fecal coliforms is required when |                               |
| the M value for [EB]{.mark}          |                               |
| ~~coliforms~~ is less than ~~or      |                               |
| equal to~~ 3.0~~5~~.                 |                               |
|                                      |                               |
| ^7^ None detected.                   |                               |
|                                      |                               |
| ^8^ *[B. cereus]{.mark}* testing     |                               |
| must be performed only if the APC    |                               |
| exceeds [1000]{.mark} ~~100~~ CFU/g  |                               |
| [(except for probiotic infant        |                               |
| formulas)]{.mark}.                   |                               |
+--------------------------------------+-------------------------------+

106.55(d) Manufacturers shall make and retain records, in accordance
with §106.100(e)(5)(ii) and (f)(7), on the testing of infant formulas
for microorganisms.

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

106.60(a) Manufacturers shall examine packaged and labeled infant
formula during finishing operations to ensure that containers and
packages in the lot have the correct label, the correct use-by date, and
the correct code established under §106.80.

106.60(b) Labels shall be designed, printed, and applied so that the
labels remain legible and attached during the conditions of processing,
storage, handling, [and]{.mark} distribution~~, and use~~.

106.60(c) ~~All infant formulas held in a single package shall be the
same product bearing the same code, established under Sec. 106.80.~~
Packaging used to hold multiple containers of [the same type of]{.mark}
infant formula shall be labeled with the product name, the name of the
manufacturer[, distributor]{.mark} or shipper, and the [lot number.
Packaging used to hold containers of different types of infant formula
shall be labeled with the product names, the name of the manufacturer,
responsible party or shipper, a lot number]{.mark} code [that can serve
to identify the contents, and an expiration date reflecting a shelf life
no greater than the container exhibiting the shortest expiration
date.]{.mark}

106.70 Controls on the release of finished infant formula.

106.70(a) The manufacturer [or responsible party]{.mark} shall hold, or
maintain under its control, each batch of infant formula until it
determines that the batch meets ~~all of its specifications, including
those adopted to meet~~ the requirements of ~~106.55 on microbiological
contamination and 106.91(a) on quality control procedures, and releases
the batch for distribution.~~ [21 CFR Part 106.]{.mark}

106.70(b) Each batch of infant formula that fails to meet the
~~manufacturer\'s specifications~~ [requirements of Sec.
106.70(a)]{.mark} shall be rejected. Although the batch may be
reprocessed, any batch of infant formula that is reprocessed shall be
shown to meet the requirements of Sec. 106.70(a) before it is released.

106.70(c) An individual qualified by training or experience shall
conduct an investigation of a finding that a batch of infant formula
fails to meet any manufacturer\'s ~~specifications.~~ [or responsible
party\'s specifications in order to ensure that such failure does not
lead to the release of adulterated product.]{.mark}

106.80 Traceability.

106.80(a) Manufacturers shall ensure traceability by coding infant
formulas in conformity with the coding requirements prescribed in
§113.60(c) of this chapter for thermally processed low-acid foods
packaged in hermetically-sealed containers, except as provided in
paragraph (b) of this section.

106.80(b) Batches of powdered infant formula that are manufactured in
stages over more than 1 day, in lieu of being coded in accordance with
§113.60(c) of this chapter, may 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
batch, 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.

90. **Audits of current good manufacturing practice.**

Manufacturers of an infant formula, or an agent of such manufacturers,
shall conduct regularly scheduled audits to determine whether the
manufacturer has complied with the current good manufacturing practice
regulations in this subpart. These audits shall be performed by an
individual who, as a result of education, training, and experience, is
knowledgeable ~~in all aspects~~ of infant formula production and of the
agency\'s regulations concerning good manufacturing practices but who
has no direct responsibility for the matters being audited.

**Subpart C\--Quality Control Procedures**

**106.91 General quality control.**

106.91(a) *Nutrient testing to ensure that each batch of infant formula
provides nutrients in accordance with Sec. 107.100.* Manufacturers [or
responsible parties]{.mark} shall test each batch as follows:

106.91(a)(1) Each nutrient premix used in the manufacture of an infant
formula shall be tested for each nutrient that the manufacturer is
relying on the premix to provide to ensure that the premix is in
compliance with the manufacturer\'s specifications;

106.91(a)(2) During the manufacturing process, after the addition of the
premix, or at the final-product-stage but before distribution, each
batch 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 batch of infant formula.

106.91(a)(3) At the final-product-stage, before distribution of an
infant formula, each batch shall be tested for vitamins A, C, E, and
thiamin.

106.91(a)(4) During the manufacturing process or at the
final‑product‑stage, before distribution, each batch shall be tested for
~~all nutrients~~ [each nutrient]{.mark} required to be included in such
formula under 107.100 of this chapter ~~and for any nutrient added by
the manufacturer for which testing is not~~ [if the presence of that
nutrient in the batch has not been confirmed pursuant to testing]{.mark}
conducted for compliance with paragraphs (a)(1)[, (a)(2)]{.mark} or
(a)(3) of this section. [Such testing shall be conducted using validated
test methods.]{.mark}

106.91(b) *~~Stability testing~~ [Testing of finished product to confirm
that the infant formula provides nutrients in accordance with Sec.
107.100.]{.mark}* [Manufacturers or responsible parties shall test
finished product as follows:]{.mark}

[106.91(b)(1) *Periodic Analysis*]{.mark}. Every 3 months, manufacturers
[or responsible parties]{.mark} shall collect representative samples
~~from the final‑product‑stage~~ [of infant formula]{.mark} of one batch
of each physical form (powder, ready‑to‑feed, or concentrate) of each
infant formula, at each manufacturing facility. The manufacturer shall
test these samples for each nutrient required under Sec. 107.100 of this
chapter ~~and for any nutrient added by the manufacturer. The frequency
of such testing shall be at the beginning, midpoint, and end of~~ [that
was not tested directly at the finished product stage pursuant to
106.91(a)(4).]{.mark}

[106.91(b)(2) *Stability testing*. Using representative samples
collected from finished product batches, the manufacturer shall conduct
stability analysis for selected labile nutrients]{.mark} ~~The frequency
of such testing shall be at the beginning, midpoint, and end of~~ [with
sufficient frequency to substantiate the maintenance of nutrient content
consistent]{.mark} ~~throughout the shelf life of the infant formula
and, depending on the nutrient and its stability within the matrix of
the formulation, with additional frequency as is necessary to ensure
that such formula complies~~ [with section 412 of the Federal Food,
Drug, and Cosmetic Act (the act) throughout the shelf life of the infant
formula.]{.mark}~~; except that:~~

106.91(b)(~~1~~[3]{.mark}) If the infant formula is a new infant
formula, manufacturers [or responsible parties]{.mark} shall collect a
representative sample from the final-product‑stage of each physical form
(powder, ready‑to‑feed, or concentrate) of the first batch of the new
infant formula and test these samples according to the requirements of
this section; and

106.91(b)(~~2~~[4]{.mark}) If an infant formula has been changed in
formulation or in processing in a way that does not make it a new infant
formula but that may affect whether it is adulterated under section
412(a) of the act, the manufacturer [or responsible party]{.mark} shall
collect a representative sample from the final-product-stage of each
physical form (powder, ready‑to‑feed, or concentrate) of the first batch
of the infant formula and shall test these samples ~~according to the
frequency required by this section~~ for each nutrient that has been or
may have been [significantly and adversely]{.mark} affected by the
change. [The manufacturer or responsible party shall determine if
stability testing should be conducted for such a change and the
frequency of such testing, if deemed necessary.]{.mark}

106.91(c) Quality control records. Manufacturers shall make and retain
quality control records in accordance with Sec. 106.100(e)(5)(i) and
(f)(7).

106.92 Audits of quality control procedures.

A manufacturer ~~of an infant formula~~, or an agent ~~of such a
manufacturer~~ [thereof]{.mark}, shall conduct regularly scheduled
audits[, according to its established practice,]{.mark} to determine
whether the manufacturer has complied with the 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 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. These audits shall
be performed by an individual who, as a result of education, training,
and experience, is knowledgeable ~~in all aspects~~ of infant formula
production and of the agency\'s regulations concerning quality control
procedures but who has no direct responsibility for the matters being
audited.

**Subpart D\--Conduct of Audits.**

**106.94 Audit plans and procedures.**

106.94(a) Manufacturers shall develop and follow a written audit plan
that is available at the manufacturing facility for FDA inspection.

106.94(b) The audit plan shall include audit procedures that set out the
methods the manufacturer [or responsible party]{.mark} uses to determine
whether the facility is operating in accordance with current good
manufacturing practice, with the quality control procedures that are
necessary to assure that an infant formula provides nutrients in
accordance with section 412(b) and (i) of the Federal Food, Drug, and
Cosmetic Act, and in a manner designed to prevent adulteration of the
infant formula.

106.94(c) The audit procedures shall include, but not be limited to:

106.94(c)(1) An evaluation of the production and in-process control
system established under Sec. 106.6(b) by:

106.94(c)(1)(i) Observing the ~~production~~ [critical manufacturing
steps]{.mark} of infant formula and comparing the observed process to
the written production and in‑process control plan required under Sec.
106.6(b);

106.94(c)(1)(ii) Reviewing records of [representative batches, over
multiple days of production, of]{.mark} the monitoring of points, steps,
or stages where control is ~~deemed necessary~~ [critical]{.mark} to
prevent adulteration; and

106.94(c)(1)(iii) Reviewing records of how deviations from any
~~standard or~~ specification at points, steps, or stages where control
is deemed necessary to prevent adulteration were handled [to assure that
the review was complete]{.mark}; and

106.94(c)(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

**106.96 Quality factors in infant formulas.**

106.96(a) All infant formulas [shall meet established quality
factors]{.mark}~~, when fed to infants as a sole source of nutrition, be
of sufficient quality to meet the nutritional requirements for healthy
growth. The regulations set forth in this subpart define the minimum
quality factors for infant formulas~~.

~~106.96(b) All infant formulas shall be capable of supporting normal
physical growth of infants.~~

106.96(~~c~~[b]{.mark}) All infant formulas shall be formulated and
manufactured such that the protein is of sufficient biological quality
to meet the protein requirements of infants.

**106.97 Assurances for quality factors.**

~~106.97(a) General quality factor of normal physical growth.~~

~~106.97(a)(1) The manufacturer shall conduct an adequate and
well-controlled clinical study, 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.~~

~~106.97(a)(1)(i) The manufacturer shall:~~

~~106.97(a)(1)(i)(A) Conduct a clinical study that is no less than 4
months in duration, enrolling infants no more than 1 month old at time
of entry into the study.~~

~~106.97(a)(1)(i)(B) Collect and maintain data in the study on
anthropometric measures of physical growth, including body weight,
recumbent length, head circumference, and average daily weight
increment, and plot the data on National Center for Health Statistics
(NCHS) reference percentile body weight and body length curves. The NCHS
growth charts are incorporated by reference in accordance with 5 U.S.C.
552(a) and 1 CFR part 51. Copies are available from the Office of
Constituent Operations (HFS-565), Center for Food Safety and Applied
Nutrition, Food and Drug Administration, 200 C St. SW, Washington, DC
20204, may be examined at the Office of Special Nutritionals (HFS-456),
Center for Food Safety and Applied Nutrition, Food and Drug
Administration, 200 C St. SW, Washington, DC 20204, or the Office of the
Federal Register, 800 North Capitol St. NW, Suite 700, Washington, DC.~~

~~106.97(a)(1)(i)(C) Collect anthropometric measurements at the
beginning of the clinical study, at 2 weeks, at 4 weeks, at least
monthly thereafter, and at the conclusion of the study.~~

~~106.97(a)(1)(ii) The clinical study protocol should:~~

~~106.97(a)(1)(ii)(A) Describe the scientific basis and objectives of
the study, the planned control and treatment feeding regimens, the
entrance criteria used to enroll infants in the study, the method of
randomization used for the assignment of infants to feeding groups, the
collection of specific measurements and other data, the methods used to
limit sources of bias, and the planned methods of statistical
analysis;~~

~~106.97(a)(1)(ii)(B) Describe the necessary qualifications and
experience of investigators;~~

~~106.97(a)(1)(ii)(C) Be reviewed and approved by an Institutional
Review Board (IRB) in accordance with part 56 of this chapter. The
manufacturer shall establish procedures to obtain written informed
consent from parents or legal representatives of the infants enrolled in
the study in accordance with part 50 of this chapter;~~

~~106.97(a)(1)(ii)(D) Explain how the study population represents the
population for which the new infant formula is intended and how the
study addresses the intended conditions of use of the formula.~~

~~106.97(a)(1)(ii)(E) Describe the sample size calculations and the
power calculations and the basis for selecting the sample size and study
design;~~

~~106.97(a)(1)(ii)(F) Describe the plan to identify and evaluate any
adverse effects;~~

~~106.97(a)(1)(ii)(G) Describe the quality control procedures used to
ensure the validity and reliability of the measurements collected.~~

~~106.97(a)(1)(ii)(H) Describe and compare the composition of the test
and control formulas.~~

~~106.97(a)(1)(ii)(I) Describe the basis upon which the test formula is
appropriate for use in evaluating the formula that the manufacturer
intends to market, if the test formula used in a study is not identical
to the formula that is intended to be marketed in the United States.~~

~~106.97(a)(2) The manufacturer may request an exemption from the
requirements of paragraph (a)(1) of this section if:~~

~~106.97(a)(2)(i) The manufacturer has similar experience using an
ingredient, an ingredient mixture, or a processing method in the
production of an infant formula marketed in the United States and can
demonstrate that infant formula made with that ingredient, ingredient
mixture, or processing method meets the quality factor requirements in
Sec. 106.96;~~

~~106.97(a)(2)(ii) The manufacturer markets a formulation in more than
one form (e.g., liquid and powdered forms) and can demonstrate that 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;~~

~~106.97(a)(2)(iii) The manufacturer can demonstrate that the
requirements of paragraph (a)(1) of this section are not appropriate for
evaluation of a specific infant formula, and that an alternative method
or study design for showing that the formula supports healthy growth in
infants fed it as their sole source of nutrition is available.~~

106.97(~~b~~[a]{.mark}) Specific quality factor for protein quality of
infant formula.

106.97(~~b~~[a]{.mark})(1) The manufacturer [or responsible
party]{.mark} shall collect and maintain data that establish that the
biological quality of protein in an infant formula is sufficient to meet
the protein requirements of infants. The manufacturer [or responsible
party]{.mark} shall establish the biological quality of the protein in
its infant formula [with any AOAC approved method, including]{.mark}
~~by demonstrating that the protein source supports adequate growth
using~~ the Protein Efficiency Ratio (PER) rat bioassay described in the
\"Official Methods of Analysis of the Association of Official Analytical
Chemists,\" 16th ed., sections 43.3.04 and 43.3.05, \"AOAC Official
Method 960.48 Protein Efficiency Ratio Rat Bioassay\" which is
incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR
part 51. Copies are available from the Association of Official
Analytical Chemists, 481 North Frederick Ave., Suite 500, Gaithersburg,
MD 20857, or the Office of Special Nutritionals (HFS-456), Center for
Food Safety and Applied Nutrition, Food and Drug Administration, 200 C
St. SW, Washington, DC 20204, or may be examined at the Office of the
Federal Register, 800 North Capitol St. NW, Washington, DC. If the
manufacturer is unable to conduct a PER rat bioassay because of the
composition of the protein in the formula, then it shall demonstrate
that the amino acid composition of the protein meets the known amino
acid requirements of infants for whom the formula is intended.

106.97(~~b~~[a]{.mark})(2) The manufacturer may request an exemption
from the requirements of paragraph (b)(1) of this section if:

106.97(~~b~~[a]{.mark})(2)(i) The protein source, including any
processing method used to produce the protein source, is already used in
another infant formula marketed in the United States, manufactured by
the same manufacturer, and the manufacturer can demonstrate that such
infant formula meets the quality factor requirements prescribed in Sec.
106.96;

106.97(~~b~~[a]{.mark})(2)(ii) The protein source, including any
processing methods used to produce the protein source, is not a major
change from the infant formula it replaces, and the manufacturer can
demonstrate that the infant formula it replaces meets the quality factor
requirements prescribed in Sec. 106.96.

In newly redesignated subpart F, Sec 106.100 is amended by revising
paragraphs (e), (f), (g),(j) and (k)(3), and by removing and reserving
paragraph (h) to read as follows:

106.100 Records

\* \* \* \*

106.100(e) *Batch production and control records*. For each batch of
infant formula, manufacturers shall prepare and maintain records that
include complete information relating to the production and control of
the batch. ~~These records shall include but are not limited to:~~ [The
records that are necessary under this paragraph are:]{.mark}

106.100(e)(1) The master manufacturing order. The master manufacturing
order shall include ~~but is not limited to~~:

106.100(e)(1)(i) The significant steps in the production of the batch
and the date on which each significant step occurred;

106.100(e)(1)(ii) The identity of [the major]{.mark} equipment ~~and
processing lines~~ [systems]{.mark} used in producing the batch, if the
plant in which the formula is made includes more than one ~~set of~~
equipment ~~or more than one processing line~~ [system]{.mark};

106.100(e)(1)(iii) The identity of each batch or lot of ingredients,
containers, and closures used in producing the batch of formula;

106.100(e)(1)(iv) The amount of each ingredient to be added to the batch
of infant formula and a check (verification) that the correct amount was
added; and

106.100(e)(1)(v) Copies of all ~~labeling~~ [primary container
labels]{.mark} used and the results of examinations conducted during the
finishing operations to provide assurance that containers and packages
in the lot have the correct label.

106.100(e)(2) Any deviations from the master manufacturing order and any
~~corrective~~ [specific]{.mark} actions taken [to adjust or correct a
batch in response to a deviation]{.mark} ~~because of the deviations~~.

106.100(e)(3) Documentation, in accordance with Sec. 106.6(c), of the
monitoring at any point, step, or stage in their production process
where control is deemed ~~necessary~~ [critical]{.mark} to prevent
adulteration. ~~These records~~ [The records that are necessary under
this paragraph]{.mark} shall include~~, but not be limited to~~:

106.100(e)(3)(i) A list of the ~~standards or~~ specifications
established at each point, step, or stage in their production process
where control is deemed necessary ~~to prevent adulteration including
documentation of the scientific basis for each standard or
specification;~~ [by the manufacturer.]{.mark}

106.100(e)(3)(ii) The actual values obtained during the monitoring
operation, any deviations from established ~~standards or~~
specifications, and any ~~corrective~~ [specific]{.mark} actions taken
[to adjust or correct a batch in response to a deviation]{.mark};

106.100(e)(3)(iii) Identification of the person monitoring each point,
step, or stage in their production process where control is deemed
necessary to prevent adulteration.

106.100(e)(4) The conclusions and follow-up, along with the identity, of
the individual qualified by training or experience who investigated:

106.100(e)(4)(i) Any deviation from the master manufacturing order and
any ~~corrective~~ [specific]{.mark} actions taken [to adjust or correct
a batch in response to a deviation]{.mark};

106.100(e)(4)(ii) A finding that a batch or any of its ingredients
failed to meet the infant formula manufacturer\'s specifications; and

~~106.100(e)(4)(iii) A failure to meet any specification or standard at
any point, step, or stage in the production process where control is
deemed necessary to prevent adulteration.~~

106.100(e)(5) The results of all testing performed on the batch of
infant formula, including testing on the in‑process batch, at the
final‑product stage~~,~~ and on finished ~~product throughout the shelf
life of the~~ product. The results recorded shall include ~~but are not
limited to~~:

106.100(e)(5)(i) The results of all quality control testing conducted,
in accordance with Sec. 106.91(a) and (b), to verify that each nutrient
required by Sec. 107.100 of this chapter is present in each batch of
infant formula at the level required by Sec. 107.100, and that any
nutrient added by the manufacturer is present at the appropriate level
with:

106.100(e)(5)(i)(A) A summary table identifying the stages of the
manufacturing process at which the nutrient analysis for each required
nutrient under §106.91(a) is conducted, and

~~106.100(e)(5)(i)(B) A summary table on the stability testing program,
including the nutrients tested and the frequency of testing of nutrients
throughout the shelf life of the product under 106.91(b); and~~

106.100(e)(5)(ii) For powdered infant formula, the results of any
testing conducted in accordance with §106.55(b) to verify compliance
with the microbiological quality standards in §106.55(c).

106.100(f) Manufacturers shall make and retain all [the following
necessary]{.mark} records pertaining to current good manufacturing
practice as described in subpart B of this part~~, including but not
limited to~~:

106.100(f)(1) Records, in accordance with §106.20(f)(3), of the
frequency and results of testing of the water used in the production of
infant formula;

106.100(f)(2) Records, in accordance with §106.30(d), of accuracy checks
of instruments and controls. A certification of accuracy of any known
reference standard used and a history of recertification shall be
maintained. At a minimum, such records shall specify the instrument or
control being checked, the date of the accuracy check, the standard
used, the calibration method used, the results found, any actions taken
if the instrument is found to be out of calibration, and the initials or
name of the individual performing the test. If calibration of an
instrument (testing for accuracy against a known reference standard)
shows that a specification ~~or standard~~ at a point, step, or stage in
the production process where control is deemed necessary to prevent
adulteration has not been met, a written evaluation of all affected
product, and any actions that need to be taken with respect to that
product, shall be made.

106.100(f)(3) Records, in accordance with §106.30(e)(3)(ii), of the
temperatures monitored for cold storage compartments and thermal
processing equipment.

106.100(f)(4) Records, in accordance with Sec. 106.30(f), on equipment
cleaning, sanitizing~~,~~ and [critical]{.mark} maintenance that show
the date and time of such cleaning, sanitizing~~,~~ and
[critical]{.mark} maintenance ~~and the lot number of each batch of
infant formula processed between equipment startup and shutdown for
cleaning, sanitizing, and maintenance~~. The person performing and
checking the cleaning, sanitizing~~,~~ and [critical]{.mark} maintenance
shall date and sign or initial the record indicating that the work was
performed.

[Delete]{.mark}

[or]{.mark}

106.100(f)(5) Records, in accordance with Sec. 106.35(c), on all
automatic (mechanical or electronic) equipment used in the production or
quality control of infant formula. These records shall include ~~but not
be limited to~~:

~~106.100(f)(5)(i) A list of all systems used with a description of
computer files and the inherent limitations of each system;~~

~~106.100(f)(5)(ii) A copy of all software used;~~

~~106.100(f)(5)(iii) Records that document installation, calibration,
testing or validation, and maintenance of the systems used;~~

~~106.100(f)(5)(iv) A list of all persons authorized to create or modify
software;~~

~~106.100(f)(5)(v) Records that document modifications to software,
including the identity of the person who modified the software;~~

~~106.100(f)(5)(vi) Records that document retesting or revalidation of
modified systems; and~~

~~106.100(f)(5)(vii) A backup file of data entered into a computer or
related system. The backup file shall consist of a hard copy or
alternative system, such as duplicate diskettes, tapes, or microfilm,
designed to ensure that backup data are exact and complete, and that
they are secure from alteration, inadvertent erasures, or loss.~~

106.100(f)(6) Records, in accordance with 106.40(g), on ingredients,
containers, and closures used in the manufacture of infant formula. [The
records that are necessary under this paragraph are]{.mark} ~~These
records shall include, but are not limited to~~:

106.100(f)(6)(i) The identity and quantity of each lot of ingredients,
containers, and closures;

106.100(f)(6)(ii) The name of the supplier;

106.100(f)(6)(iii) The supplier\'s lot numbers;

106.100(f)(6)(iv) The name and location of the manufacturer of the
ingredient, container, and closure, if different from the supplier;

106.100(f)(6)(v) The date of receipt;

106.100(f)(6)(vi) The receiving code as specified; and

106.100(f)(6)(vii) The results of any test or examination (including
retesting and reexamination) performed on the ingredients, containers,
and closures and the conclusions derived therefrom and the disposition
of all ingredients, containers, or closures.

106.100(f)(7) A full description of the methodology used to test
powdered infant formula to verify compliance with the microbiological
quality standards of §106.55(c) and the methodology used to do quality
control testing, in accordance with §106.91(a) and (b).

[106.100(f)(8) Results of stability testing performed pursuant to
106.91(b)(2).]{.mark}

106.100(g) The manufacturer shall maintain all records pertaining to
[the manufacturer\'s]{.mark} distribution of the infant formula,
including records ~~that show that~~ [for]{.mark} products produced for
export only ~~are exported. Such records shall include, but not be
limited to, all~~. [The records required under this paragraph are those
providing the]{.mark} information and data necessary to effect and
monitor recalls of the manufacturer\'s infant formula products in
accordance with subpart E of part 107 of this chapter.

106.100(h) \[Reserved\]

\* \* \* \* \*

106.100(j) The manufacturer shall make and retain records pertaining to
regularly scheduled audits, including the audit plans and procedures,
the findings of the audit, and a listing of any changes made in response
to these findings. The manufacturer shall make readily available for
authorized inspection the audit plans and procedures and a statement of
assurance that the regularly scheduled audits are being conducted. The
findings of the audit and any changes made in response to these findings
shall be maintained for the time period required under §106.100(n), but
need not be made available to FDA.

106.100(k)(3) When there is a reasonable possibility of a causal
relationship between the consumption of an infant formula and an
infant\'s death, the ~~manufacturer~~ [responsible party]{.mark} shall,
within 15 days of receiving such information, conduct an investigation
and notify the agency as required in Sec. 106.150.

**Subpart G\--Registration, Submission, and Notification Requirements**

**106.110 New infant formula registration.**

106.110(a) Before a new infant formula may be introduced or delivered
for introduction into interstate commerce, the manufacturer of such
formula shall register with the Food and Drug Administration, Center for
Food Safety and Applied Nutrition, Office of Special Nutritionals,
Division of Programs and Policy Enforcement (HFS-455), Infant Formula
Coordinator, 200 C St. SW, Washington, DC 20204. An original and two
copies of this registration shall be submitted.

106.110(b) The new infant formula registration shall include:

106.110(b)(1) The name of the new infant formula,

106.110(b)(2) The name of the manufacturer [and of the responsible party
if other than the manufacturer]{.mark},

106.110(b)(3) The place of business of the manufacturer~~,~~ and [of the
responsible party if other than the manufacturer]{.mark}, and

106.110(b)(4) ~~All~~ [The names and addresses of all]{.mark}
establishments at which the manufacturer [or responsible party]{.mark}
intends to manufacture such new infant formula.

**106.120 New infant formula submission.**

106.120(a) At least 90 days before a new infant formula is introduced or
delivered for introduction into interstate commerce, a ~~manufacturer~~
[responsible party]{.mark} shall submit notice of its intent to do so to
the Food and Drug Administration at the address given in Sec.
106.110(a). An original and two copies of the notice of its intent to do
so shall be submitted.

106.120(b) The new infant formula submission shall include:

106.120(b)(1) The name and physical form (e.g., powder, ready-to feed,
or concentrate) of the infant formula;

106.120(b)(2) An explanation of why the formula is a new infant formula;

106.120(b)(3) The quantitative formulation of each form of the infant
formula that is the subject of the notice in units per volume (for
liquid formulas) or units per dry weight (for powdered formulas). When
applicable, the submission shall include a description of any
reformulation of the infant formula, including a listing of each new or
changed ingredient and a discussion of the effect of such changes on the
nutrient levels in the formulation;

106.120(b)(4) A description, when applicable, of any change in
processing of the infant formula. ~~Such description shall identify the
specific change in processing, including side‑by‑side, detailed
schematic diagrams comparing the new processing to the previous
processing (including processing times and temperatures);~~

106.120(b)(5) Assurance that the infant formula will not be marketed
unless the formula meets the quality factor requirements of section
412(b)(1) of the Federal Food, Drug, and Cosmetic Act (the act) and the
nutrient content requirements of section 412(i) of the act.

106.120(b)(5)(i) Assurance that the formula meets the quality factor
requirements, which are set forth in subpart E of this part, shall be
provided by a submission that complies with Sec. 106.121.

106.120(b)(5)(ii) Assurance that the formula complies with the nutrient
content requirements, which are set forth in §107.100 of this chapter,
shall be provided by a statement assuring that the formula will not be
marketed unless it meets the nutrient requirements of §107.100 of this
chapter, as demonstrated by testing required under subpart C of this
part;

106.120(b)(6) Assurance that the processing of the infant formula
complies with section 412(b)(2) of the act. Such assurance shall include
but not be limited to:

[106.120(b)(6)(i) A responsible party that has not previously
manufactured infant formula for sale in the U.S. market must support the
premarket notification with a clinical study.]{.mark}

[]{.mark}

[106.120(b)(6)(ii) Clinical studies also may be necessary when a current
manufacturer or responsible party predicts, based on its experience or
theory, that a major change could have possible significant adverse
impact on bioavailability of nutrients and when chemical testing or
other scientific information are unavailable to rule out such an adverse
impact.]{.mark}

[]{.mark}

[106.120(b)(6)(iii) The manufacturer shall determine the scope, degree
and complexity of any needed clinical testing, on a case-by-case basis.
The particular elements of the study shall take into account Guidelines
issued by FDA regarding clinical study protocol and design and endpoints
needed to support potential claims.]{.mark}

106.120(b)(~~6~~[7]{.mark}) Assurance that the processing of the infant
formula complies with section 412(b)(2) of the act. Such assurance shall
include but not be limited to:

106.120(b)(~~6~~[7]{.mark})(i) A statement that the formula will be
produced in accordance with subparts B and C of this part;

~~106.120(b)(6)(ii) The basis on which each ingredient meets the
requirements of 106.40(a), e.g., that it is an approved food additive,
that it is authorized by a prior sanction issued by the agency, or that
it is GRAS for its intended use. Any claim that an ingredient is GRAS
shall be supported by a citation to the agency\'s regulations or by an
explanation, including a list of published studies and a copy of those
publications, for why, based on the published studies, there is general
recognition of the safety of the use of the ingredient in infant
formula.~~

106.120(c) For products for export only [and in compliance with Section
801(e) of the Act, the information under paragraph (b) of this section
is not required and need not be submitted]{.mark}~~, a manufacturer may
submit, in lieu of the information required under paragraph (b) of this
section, a statement that the infant formula meets the specifications of
the foreign purchaser, does not conflict with the laws of the country to
which it is intended for export, is labeled on the outside of the
shipping package to indicate that it is intended for export only, and
will not be sold or offered for sale in domestic commerce~~.

106.120(d) The submission will not constitute notice under section 412
of the act unless it complies fully with paragraph (b) of this section,
and the information that it contains is set forth in a manner that is
readily understandable. The agency will notify the submitter [within 10
working days]{.mark} if the notice is not ~~adequate~~ [complete]{.mark}
because it does not meet the requirements of section 412(c) and (d) of
the act.

106.120(e) If a new infant formula submission is ~~adequate~~ [complete
and includes all requirements of 106.120(b)]{.mark}, FDA will
acknowledge its receipt and notify the ~~manufacturer~~
[submitter]{.mark} of the date of [the]{.mark} receipt. The date that
the agency receives the new infant formula submission is the filing date
for the submission. The manufacturer shall not market the new infant
formula before the date that is 90 days after the filing date.

106.120(f) If the ~~manufacturer~~ [submitter]{.mark} provides
additional information in support of a new infant formula submission,
the agency will determine whether the additional information is a
substantive amendment to the new infant formula submission. If the
agency determines that the new submission is a substantive amendment,
FDA will assign the new infant formula submission a new filing date. FDA
will acknowledge receipt of the additional information [within five
working days]{.mark} and, when applicable, notify the ~~manufacturer~~
[submitter]{.mark} of the new filing date, which is the date of receipt
by FDA of the information that constitutes the substantive amendment to
the new infant formula submission.

**106.121 Quality factor submission.**

To provide assurance that ~~an~~ [a new]{.mark} infant formula meets the
quality factor requirements set forth in subpart E of this part, the
~~manufacturer~~ [responsible party]{.mark} shall submit the following
data and information:

106.121(a) An explanation, in narrative form, setting forth how all
quality factor requirements of subpart E of this part have been met.

~~106.121(b) Records that contain the information required by proposed
Sec. 106.97(a)(1)(i) and (a)(1)(ii) collected during the study for each
infant enrolled in the study. The records shall be identified by subject
number, age, feeding group, gender, and study day of collection.~~

~~106.121(c)(1) Statistical evaluation for all measurements, including:
Group means, group standard deviations, and measures of statistical
significance for all measurements for each feeding group at the
beginning of the study and at every point where measurements were made
throughout the study.~~

~~106.121(c)(2) Calculation of the statistical power of the study at its
completion.~~

~~106.121(d) A report on attrition and on all occurrences of adverse
events during the study, which shall include:~~

~~106.121(d)(1) Identification of the infant by subject number and
feeding group and a complete description of the adverse event, including
comparisons of the frequency and nature of occurrence in each feeding
group and information on the health of the infant during the course of
the study, including the occurrence and duration of any illness;~~

~~106.121(d)(2) A clinical assessment, by a health care provider, of the
infant\'s health during each suspected adverse event;~~

~~106.121(d)(3) A complete listing of all infants who did not complete
the study, including the infant\'s subject number and the reason that
each infant left the study.~~

~~106.121(e) The results of the Protein Efficiency Ratio, in accordance
with Sec. 106.97(b).~~

106.121(~~f~~[b]{.mark}) A statement ~~certifying~~ [of
assurance]{.mark} that the manufacturer [or responsible party]{.mark}
has collected and considered all information and data concerning the
ability of the infant formula to meet the quality factor requirements,
and that the manufacturer [or responsible party]{.mark} is not aware of
any information or data that would show that the formula does not meet
the quality factors requirements.

**106.130 Verification submission.**

106.130(a) [Unless subject to 106.120(c) \[proposed by IFC to be moved
and become 106.140(d)\],]{.mark} ~~M~~manufacturers [or responsible
parties]{.mark} shall, after the first production and before the
introduction into interstate commerce of the new infant formula, 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 (the~~ act~~)~~ and is not adulterated. An
original and two copies of this verification shall be submitted.

106.130(b) The verification submission shall include the following
information:

106.130(b)(1) The name of the new infant formula; the filing date for
the new infant formula submission, in accordance with Sec. 106.120, for
the subject formula; and the identification number assigned by the
agency[, if available,]{.mark} to the new infant formula submission;

106.130(b)(2) 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 notification and for which the
manufacturer [or responsible party]{.mark} provided assurances in
accordance with the requirements of Sec. 106.120;

106.130(b)(3) A summary of test results of the level of each nutrient
required by §107.100 of this chapter and any nutrient added by the
manufacturer in the formula, presented in units per 100 kilocalories at
the final-product-stage.

[106.130(b)(4) If testing for protein biological quality is needed, an
assurance that the PER or other test has commenced, and that the results
will be forwarded to FDA within 10 working days of their receipt by the
manufacturer or responsible party as a supplement to the verification
submission.]{.mark}

106.130(b)(~~4~~5) ~~A certification that the manufacturer has~~ [An
assurance by the responsible party that all manufacturers have]{.mark}
established current good manufacturing practices including quality
control procedures and in‑process controls, including testing required
by current good manufacturing practice, designed to prevent adulteration
of this formula in accordance with subparts B and C of this part.

106.130(c) The submission will not constitute written verification under
section 412(d)(2) of the act when any data prescribed in paragraph (b)
of this section are lacking or are not set forth so as to be readily
understood. In such circumstances the agency will notify the submitter
[within five working days]{.mark} that the notice is not ~~adequate~~
[complete]{.mark}.

**106.140 Submission[s for Minor Changes in the Infant Formula]{.mark}
~~concerning a change in infant formula that may adulterate the
product~~.**

106.140(a) When a manufacturer makes a change in the formulation or
processing of the formula that [is determined to be a notifiable minor
change because the manufacturer or responsible party determines
it]{.mark} may affect whether the formula is adulterated under section
412(a) of the ~~Federal Food, Drug, and Cosmetic Act (the act)~~
[act]{.mark}, it shall, before the first processing of such formula,
make a submission to the Food and Drug Administration at the address
given in Sec. 106.110(a). An original and two copies shall be
submitted.106.140(b) The submission shall include:

106.140(b)(1) The name and physical form of the infant formula (i.e.,
powder, ready-to-feed, or concentrate);

106.140(b)(2) An explanation of why the change ~~in formulation or
processing~~ may affect whether the formula is adulterated [and
assurance that the formula will not be introduced into interstate
commerce unless it is not adulterated]{.mark};

106.140(b)(3) A submission that complies with §106.120(b)(3), (b)(4),
(b)(5), and (b)(6). When appropriate, a statement to the effect that the
information required by §106.120(b)(3), (b)(4), (b)(5), or (b)(6) has
been provided to the agency previously and has not been affected by the
changes that is the subject of this submission, together with the
identification number assigned by the agency to the relevant infant
formula submission, may be provided in lieu of such submission.

106.140(c) The submission will not constitute notice under section 412
of the act unless it complies fully with paragraph (b) of this section,
and the information that it contains is set forth in a manner that is
readily understandable. The agency will [promptly acknowledge receipt
and]{.mark} notify the submitter if the notice is not adequate because
it does not meet the requirements of section 412(d)(3) of the act.

[106.140(d) The requirements of 106.140 do not apply to products legally
exported under §801(e) of the act.]{.mark}

106.150 Notification of an adulterated or misbranded infant formula.

106.150(a) A manufacturer [or responsible party]{.mark} shall promptly
notify FDA in accordance with paragraph (b) of this section, when the
manufacturer [or responsible party]{.mark} has knowledge (that is, the
actual knowledge that the manufacturer [or responsible party]{.mark}
had, or the knowledge which a reasonable person would have had under
like circumstances or which would have been obtained upon the exercise
of due care) that reasonably supports the conclusion that an infant
formula that has been processed by the manufacturer [or responsible
party]{.mark} and that has left an establishment subject to the control
of the manufacturer [or responsible party]{.mark}:

106.150(a)(1) May not provide the nutrients required by section 412(i)
of the act or by regulations issued under section 412(i)(2); or

106.150(a)(2) May be otherwise adulterated or misbranded. [In the case
of \"adulteration\" based on a failure to follow GMPs, 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.]{.mark}

106.150(b) The notification made according to paragraph (a) of this
section shall be made by telephone, to the Director of the appropriate
Food and Drug Administration district office. After normal business
hours (8 a.m. to 4:30 p.m.), FDA\'s emergency number, 202‑857‑8400,
shall be used. The manufacturer [or responsible party]{.mark} shall send
written confirmation of the notification to the Food and Drug
Administration, Center for Food Safety and Applied Nutrition, Office of
Special Nutritionals, Division of Programs and Policy Enforcement
(HFS‑455), Infant Formula Coordinator, 200 C St. SW, Washington, DC
20204, and to the appropriate Food and Drug Administration district
office specified in Sec. 5.115 of this chapter.

107.1 Status and applicability of the regulations in part 107.

107.1(a) The criteria set forth in subpart B of this part describes the
labeling requirements applicable to infant formula under section 403 of
the Federal Food, Drug, and Cosmetic Act (the act). Failure to comply
with any regulation in subpart B of this part will render an infant
formula misbranded under that section of the act. Acceptable as
proposed.

107.1(b) The criteria set forth in subpart C of this part describes the
terms and conditions for the exemption of an infant formula from the
requirements of section 412(a), (b), and (c) of the act. Failure to
comply with any regulations in subpart C of this part will result in the
withdrawal of the exemption given under section 412(h)(1) of the act.

107.1(c) Subpart D of this part sets forth the nutrient requirements for
infant formula under section 412(i) of the act. Failure to comply with
any regulation in subpart D of this part will render an infant formula
adulterated under section 412(a)(1) of the act.

**107.10 Nutrient Information.**

107.10(a) \* \* \*

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

107.240 Notification requirements.

107.240(a) Telephone report. When a determination is made that an infant
formula is to be recalled, the recalling firm shall telephone within 24
hours the appropriate Food and Drug Administration district office
listed in §5.115 of this chapter and shall provide relevant information
about the infant formula that is to be recalled.

107.240(b) Initial written report. Within 14 days after the recall has
begun, the recalling firm shall provide a written report to the
appropriate Food and Drug Administration district office. The report
shall contain relevant information, including the following cumulative
information concerning the infant formula that is being recalled:

107.240(b)(1) Number of consignees notified of the recall and date and
method of notification, including recalls required by §107.200,
information about the notice provided for retail display and the request
for its display.

107.240(b)(2) Number of consignees responding to the recall
communication and quantity of recalled infant formula on hand at the
time it was received.

107.240(b)(3) Quantity of recalled infant formula returned or corrected
by each consignee contacted and the quantity of recalled infant formula
accounted for.

107.240(b)(4) Number and results of effectiveness checks that were made.

107.240(b)(5) Estimated timeframes for completion of the recall.

107.240(c) Status reports. The recalling firm shall submit to the
appropriate Food and Drug Administration district office a written
status report on the recall at least every 14 days until the recall is
terminated. The status report shall describe the steps taken by the
recalling firm to carry out the recall since the last report and the
results of these steps.

**107.250 Termination of an infant formula recall**

The recalling firm may submit a recommendation for termination of the
recall to the appropriate Food and Drug Administration district office
listed in §5.115 of this chapter for transmittal to the Division of
Enforcement (HFS-605), Office of Field Programs, Center for Food Safety
and Applied Nutrition, for action. Any such recommendation shall contain
information supporting a conclusion that the recall strategy has been
effective. The agency will respond within 15 days of receipt by the
Division of Enforcement (HFS-605), Office of Field Programs, Center for
Food Safety and Applied Nutrition, of the request for termination. The
recalling firm shall continue to implement the recall strategy until it
receives final written notification from the agency that the recall has
been terminated. The agency will send such notification, unless it has
information, from FDA\'s own audits or from other sources demonstrating
the recall has not been effective. The agency may conclude that a recall
has not been effective if:

[^1]: Where changes are suggested to the FDA Proposed Regulation, words
    that IFC suggests deleting are shown by strike-through and words
    that IFC suggests adding are shown by shading. "Delete or" prior to
    a paragraph indicates IFC's preference that the language be deleted;
    the alternative suggested language that follows is provided in case
    FDA disagrees with the deletion recommendation.