infants. Without such information, FDA is not persuaded to establish a
quality factor for iron and to require an animal test to demonstrate
the bioavailability of iron in infant formula.
    (Comment 292) Several comments that supported inclusion of a
quality factor for iron concluded that serum ferritin (i.e., a stage 1
measurement of iron status) would be the appropriate quality factor
measurement because if ferritin is sufficient in the infant, there is
no risk that stage 2 or 3 iron status will be reached. The comment
further suggested that a measurement of ferritin alone would make
studies more efficient, cost effective, and less invasive.
    (Response) FDA agrees that serum ferritin is a very useful tool for
assessing iron nutritional status. However, as FDA noted in the
proposed rule (61 FR 36154 at 36182), healthy, full-term infants are
usually born with adequate iron stores to maintain normal iron status
for the first 3 to 4 months of life--the period of time that a growth
monitoring study will be conducted. Moreover, the serum ferritin
assessment requires an invasive procedure (blood draw). For these
reasons, FDA declines to establish the measurement of ferritin as a
quality factor requirement for new infant formulas.
    For the foregoing reasons, FDA is not revising Sec.  106.96 in this
interim final rule to establish a quality factor for iron.
4. Standard Laboratory Measures
    In the 1996 proposal, FDA requested, and received, comment on
whether the collection of standard laboratory measures, such as
complete blood count (white blood cell count and red blood cell count),
hemoglobin concentration or hematocrit percentage, and serum or plasma
concentrations of albumin, urea, nitrogen, electrolytes (sodium,
potassium, and chloride), alkaline phosphatase, and creatinine, would
be useful and necessary information for determining whether a formula
causes adverse consequences that may not be reflected in the quality
factor requirements for normal physical growth (61 FR 36154 at 36184).
    (Comment 293) One comment pointed out that FDA did not propose to
make serum chemistries into quality factors and that there are
situations where the relevant clinical endpoints would be biochemical
indicators of nutritional status.
    (Response) FDA notes that the comment did not submit any data or
other information identifying the particular situations that would
require serum chemistries to evaluate the nutritional adequacy of an
infant formula or why serum chemistry evaluations should be a standard
requirement for growth monitoring studies. The growth monitoring study,
which is often conducted on an outpatient basis, evaluates the adequacy
of the formula to support normal physical growth and an infant's
tolerance of the formula. Although the AAP report (Ref. 67) recommended
that some blood tests might be useful at the conclusion of the study
period, the decision lies with those responsible for designing and
conducting the study. FDA concludes, as discussed in the 1996 proposed
rule, that it is not appropriate to require invasive procedures, such
as blood draws, as part of this interim final rule. As discussed in
this document, the Agency encourages manufacturers to evaluate each new
formulation to determine whether the nature of the particular new
formulation suggests that serum blood chemistries should be required.
Accordingly, FDA is making no change in the interim final rule in
response to this comment.
    (Comment 294) One comment stated that doing such blood work is not
a standard practice of investigators and that drawing blood would
violate the principles that the FDA cites for protecting the infant
from unnecessary testing. The comment further asserted that
establishing a requirement for drawing blood would cause many parents
to refuse to have their infants participate in a study. Thus, the
comment argued, collecting this information routinely would not be
useful and could be detrimental for the timely completion of clinical
studies.
    (Response) FDA agrees with this comment. No comments submitted in
response to the Agency's request included data or other information to
demonstrate that standard blood chemistry measures are necessary to
evaluate whether an infant formula supports normal physical growth of
infants, and without question, collecting such data would require blood
draws, which is an invasive procedure. Accordingly, FDA is not
persuaded to require these standard laboratory measures as a part of
all growth studies.
    FDA notes, however, that some or all of these measures may be
appropriate for the testing of certain formulas or for certain changes
in a particular formula. For example, if a formula is developed with an
unusual renal solute load, measures of albumin, urea, electrolytes, and
creatinine in serum may be appropriate. The Agency encourages
manufacturers to evaluate each new formulation to determine whether
testing a particular formulation requires some or all of these blood
chemistries.
    For these reasons, FDA is making no change in the interim final
rule in response to these comments.

K. Miscellaneous Comments on Quality Factors

    (Comment 295) One comment challenged the statement in the 1996
proposal (61 FR 36154 at 36179) that referred to selenium as a
``nonrequired nutrient.'' The comment asserted that selenium is an
essential nutrient for infants, i.e., a required nutrient for infants.

    (Response) FDA is aware that selenium is an essential nutrient for
infants. In the preamble to the 1996 proposal (61 FR 36154 at 36155),
FDA stated ``For the purpose of this document, the nutrients that are
required to be in infant formula under Sec.  107.100 will be referred
to as ``required nutrients.'' Thus, the term ``nonrequired'' referred
to the status of selenium on the Congressionally-mandated list of
ingredients set out in section 412(i) of the FD&C Act and established
by regulation at 21 CFR 107.100. The list of minimum and maximum
specifications for nutrients in infant formulas was most recently
revised in 1986, 3 years before establishment of a recommended dietary
allowance for selenium for infants (Ref. 60).
    Additionally, in the Federal Register of April 16, 2013 (78 FR
22442), FDA published a proposed rule to amend the regulations on
nutrient specifications and labeling for infant formula to add selenium
to the list of required nutrients and to establish minimum and maximum
levels of selenium in infant formula.
    (Comment 296) One comment agreed with FDA's proposal (61 FR 36154
at 36178) to revoke the requirement in current Sec.  106.30(c)(2) for
determination of vitamin D by a rat bioassay method.
    (Response) In this interim final rule, FDA is revoking the
requirements in current Sec.  106.30(c)(2) for the determination of
vitamin D by a rat bioassay method. As explained in the proposed rule,
this rat bioassay for vitamin D is no longer a reasonable requirement
because appropriate animals for conducting this test are difficult to
acquire (Ref. 90), and an alternate analytical method for the
determination of vitamin D in infant formulas has been approved by AOAC
(Ref. 91).

IX. Subpart F--Records and Reports

    As noted in the introductory section of this preamble, in 1991, FDA
revised subpart C in part 106, and established records and reports
requirements for infant formula (56 FR 66566, December 24, 1991). These
regulations were authorized by section 412 of the FD&C Act, as amended
by the 1986 amendments, and replaced the original records regulations
established in 1982 (47 FR 17016, April 20, 1982).
    Thereafter, in 1996, the Agency proposed additional revisions to
the infant formula records and reports regulations and proposed to
redesignate these requirements as subpart F in part 106. The proposed
requirements related to batch (production aggregate) records (proposed
Sec.  106.100(e)), records to document compliance with CGMP (proposed
Sec.  106.100(f)), infant formula distribution records (proposed Sec.
106.100(g)), and records of regularly scheduled audits (proposed Sec.
106.100(j)). As noted in the proposed rule, FDA is retaining 21 CFR
106.100(l) of the current infant formula regulations. Thus, all of the
records that are required to be maintained under this interim final
rule shall be made readily available for FDA inspection.
    FDA received a number of comments on the proposed revisions to the
records and reports requirements. These comments are summarized in this
document along with the Agency's responses.

A. General Comments on Records (Proposed Sec.  106.100)

    (Comment 297) One comment objected to the phrase that relevant
records shall ``include but are not limited to'' in proposed Sec.
106.100(e), (e)(1), (e)(3), (f), (f)(6), and (g). The comment asserted
that the required records should be limited to focus on and incorporate
the statutory reference to ``necessary'' documents, rather than the
broader language that was proposed.
    (Response) FDA is removing the phrase ``but are not limited to''
language from the proposed sections identified in the comment, but not
for the reason stated in the comment. The language is unnecessary
because the words ``include,'' ``includes,'' and ``including'' have the
connotation that the itemized list that follows is not exclusive.
    Importantly, however, the Agency did not intend to identify in the
proposed codified each and every record that may be required where
these terms appear. Section 412(b)(4)(A)(i) of the FD&C Act requires
the Secretary to establish requirements that provide for the retention
of all records ``necessary to demonstrate compliance with the good
manufacturing practices and quality control procedures. . . .''
Proposed Sec.  106.100(e), for example, would require a manufacturer to
prepare and maintain records that include ``complete information
relating to the production and control of the batch.'' Although
proposed Sec.  106.100(e) specifies certain records that must be
established and maintained under this section, this provision does not
list every record related to ``complete information relating to the
production and control of the batch.'' Thus, if a manufacturer includes
in its master manufacturing order certain documents that are related to
the production and control of a production aggregate of infant formula,
such information would be required to be maintained under this
regulation even if the documents are not expressly identified in
proposed Sec.  106.100(e)(1).
    (Comment 298) One comment asserted that the proposed documentation
requirements are very burdensome and would necessitate additional
staffing to implement. However, the comment claimed that it was
difficult to quantify the additional cost without further clarification
and that it was not possible to comment further on the estimated annual
recordkeeping burden until the regulations are finalized.
    (Response) This comment simply asserts that records requirements
are burdensome without any attempt to quantify recordkeeping costs or
to estimate the recordkeeping burden. Also, the comment included no
supporting data or information for FDA to consider and to which the
Agency could respond. Therefore, FDA is not revising the interim final
rule in response to this comment.
    (Comment 299) Another comment observed that in the proposed rule,
FDA proposes large increases in recordkeeping, which will involve
recording results for each batch (production aggregate) of ingredients,
including the source of production, the batch (production aggregate)
number, the lot (production unit) number, and analysis records of raw
materials.
    (Response) The records required by this interim final rule are
necessary to achieve the public health goals of the FD&C Act, including
the CGMP regulations, which are designed to prevent the adulteration of
infant formula caused by equipment or utensils, automatic equipment,
ingredients, containers, and closures, as well as to prevent
adulteration of formula during manufacturing, packaging, and labeling.
The comment does not challenge these goals or contradict the need for
these records. Accordingly, FDA is not revising the interim final rule
in response to this comment.
    (Comment 300) One comment claimed that under the proposed rule,
production records such as pH, temperature, solids, fat, protein, and
lactose would also have to be retained for 2 years after the expiration
date of the product and that this will be very expensive and contribute
little to the overall quality of the product. The comment also
questioned the need to retain results for 2 years following a product's
withdrawal from marketing.
    (Response) It is unclear which provision of the proposal is the
subject of this comment. The proposed rule did not contain, and the
interim final rule

does not contain, a 2-year record retention requirement.
    The comment may be referring to current 21 CFR 106.100(n), which
requires retention of production records for 1 year after the
expiration of the shelf-life of a infant formula or 3 years from the
date of its manufacture, whichever is greater. FDA did not propose any
changes to this requirement, and is making no changes to this
requirement in this interim final rule. Although the comment asserted
that required records retention would be ``very expensive,'' the
comment did not offer any data or information to quantify any added
expense. Similarly, although the comment asserts that records retention
will contribute little to the overall quality of infant formula, the
comment provided no data, information, or explanation to support its
assertion about the alleged lack of effect on product quality.
Accordingly, FDA is making no revisions to the interim final rule in
response to this comment.

B. Production Aggregate Production and Control Records (Proposed Sec.
106.100(e))

    As discussed in section IV.C, to improve the clarity of the interim
final rule and eliminate certain ambiguity and confusion, FDA is
establishing in this interim final rule new terminology to refer to the
basic volumes of formula produced by a manufacturer. The two new terms,
which are identified in Sec.  106.3 of the interim final rule, are
``production aggregate'' and ``production unit.'' In the discussion
that follows, FDA is adding the parenthetical ``(production
aggregate)'' or ``(production unit),'' as appropriate, after the word
``batch'' or ``lot'' when used in a comment summary and is substituting
the new term ``production aggregate'' or ``production unit'' for
``batch'' or ``lot,'' as appropriate, in responses to comments and
where ``batch'' or ``lot'' was used in the proposed rule.
    (Comment 301) One comment acknowledged that complete documentation
of the manufacture and release of each batch (production aggregate) of
infant formula (which proposed Sec.  106.100(e) would require) is
essential, and such documentation must be readily available for review.
However, the comment argued that compilation of such documentation into
one record for each batch (production aggregate) would be redundant and
overly burdensome to manufacturers having established documentation
review systems designed to provide retrieval of all critical
information upon request. The comment requested that the Agency clarify
whether current practices could be continued under this regulation.
    (Response) FDA is not able to respond directly to the request for
clarification concerning the continuation of current practices because
there are multiple infant formula manufacturers in the U.S. and the
practices of those manufacturers are both likely to be different and
are likely to have changed since the submission of the comment.
    Importantly, however, the Agency agrees with the comment that
establishing and maintaining complete documentation of a production
aggregate of infant formula is essential because the manufacturer, FDA,
or both may need to access and consult the records rapidly in order to
identify and resolve a problem related to the production of a
particular production aggregate before the infant formula product is
released for distribution. In establishing Sec.  106.100(e) of the
interim final rule, FDA's goal is to ensure that the complete
production aggregate documentation is immediately available and
accessible to both FDA and the manufacturer. In the case of records
maintained as hard copies, immediate availability and accessibility is
accomplished by co-locating all required records relating to a
particular production aggregate (i.e., by establishing a single,
consolidated record in one physical location). For records that are
maintained electronically, immediate availability and accessibility is
accomplished by linking electronically all required records that
pertain to the same production aggregate in a way that will permit
their instantaneous retrieval.
    The Agency disagrees that maintaining a single record for each
production aggregate would be overly burdensome to manufacturers who
have established documentation review systems that can retrieve all
critical information immediately upon the Agency's request. If such
documentation in written form is kept in a location other than the
production and control record for the particular production aggregate,
there is no way to review the entire production process during
manufacture without retrieving all of the critical information from
other records and storage locations. Similarly, if electronic records
are not properly linked, neither the producer nor FDA will have prompt
access to such records. Accordingly, FDA is clarifying the proposed
requirement in Sec.  106.100(e) of the interim final rule in response
to this comment, by amending Sec.  106.100(m) of the interim final rule
to explain that all records, no matter what their form, must be
maintained in a way that allows for immediate access.
1. Master Manufacturing Order Records
    (Comment 302) One comment objected to the requirement in proposed
Sec.  106.100(e)(1)(ii) that where a manufacturing facility has more
than one set of equipment or more than one processing line, the master
manufacturing order identify the equipment and processing lines used in
making a particular batch (production aggregate). The comment suggested
that this provision be revised to require that, in such circumstances,
the master manufacturing order include the identity of only the major
equipment systems used in producing the batch (production aggregate).
The comment argued that it is reasonable to require the identity of
major equipment systems, such as processing systems and filling lines,
if more than one is available; however, it is not reasonable to expect
every piece of processing equipment, such as every transfer line, hook-
up station, jumper, and valve, to be identified in the production
records. The comment noted that infant formula manufacturing involves
multitudes of equipment pieces and lines, so the itemization of these
for every batch (production aggregate) would require significant
resources with no practical benefits.
    (Response) FDA is not persuaded to revise Sec.  106.100(e)(1)(ii)
to limit the subject equipment to ``major equipment systems'' because
doing so may exclude equipment that, while not ``major,'' may, in the
event of a malfunction or contamination, be implicated nonetheless in
the adulteration of an infant formula. The purpose of this requirement
is in part to facilitate the identification of all production
aggregates of formula that may be affected by a particular instance of
equipment malfunction or that were produced on the same equipment as a
production aggregate that is discovered to be microbiologically
contaminated (61 FR 36154 at 36190). To achieve this purpose, a
manufacturer must identify such equipment and processing lines to
ensure, for example, that any equipment malfunctions that adulterate or
may lead to adulteration of the infant formula can be linked to any
implicated production aggregates of infant formula, which will
facilitate a material review and disposition decision and appropriate
corrective action. Similarly, it would be important to identify in the
production aggregate record any equipment components that could be a
source of adulteration but would not be readily

identified from the piece of equipment used.
    Although FDA is not making the revision requested by this comment,
the Agency is adding a phrase to Sec.  106.100(e)(1)(ii) in the interim
final rule to clarify that records of the identity of the equipment and
processing lines only need to be kept for the equipment and processing
lines for which the manufacturer has identified points, steps, or
stages in the production process where control is necessary to prevent
adulteration. Thus, Sec.  106.100(e)(1)(ii) of the interim final rule
states: ``For a manufacturing facility that has more than one set of
equipment or more than one processing line, the identity of equipment
and processing lines for which the manufacturer has identified points,
steps, or stages in the production process where control is necessary
to prevent adulteration.''
    (Comment 303) One comment requested that proposed Sec.
106.100(e)(1)(v) be revised to delete the requirement that the master
manufacturing order include copies of all labeling and substitute a
requirement that the master manufacturing order include copies of all
primary container labels used and the results of examinations during
finishing operations to provide assurance that containers and packages
have the correct label. The comment agreed with the requirement to
include a sample of the primary container label in each batch
(production aggregate) record, but asserted that including trays,
cartons, and shippers that are also considered labeling would
substantially increase the size of the batch (production aggregate)
record because the trays, cartons, and shippers are relatively bulky.
    (Response) FDA agrees that it is adequate to include in the master
manufacturing order record only a copy of the labeling used on the
immediate container of the finished production aggregate of infant
formula. Such labels are usually distinctive in appearance and, unlike
trays, cartons, and shippers, generally are the labeling on which
consumers rely when purchasing and using a formula. FDA notes that, by
definition, the word ``label'' is written, printed, or graphic matter
affixed to the immediate container of a product. 21 U.S.C. 321(k).
Accordingly, FDA is modifying Sec.  106.100(e)(1)(v) in the interim
final rule to require that the master manufacturing order include a
copy of each label used on a finished production aggregate of infant
formula and the results of examinations conducted during the finishing
operations to provide assurance that all containers have the correct
label.
    (Comment 304) One comment objected to the use of the phrase
``corrective actions'' in proposed Sec.  106.100(e)(2), (e)(3)(ii), and
(e)(4)(i) and requested that the phrase be replaced with ``specific
actions'' in each of these sections. The comment argued that, due to
timing, it is not always practical to include corrective actions in the
same batch (production aggregate) record as the documentation of
deviations. The comment explained that if the corrective action is
immediate, it would be reasonable to include documentation of the
corrective action in the batch (production aggregate) record. However,
the comment contended, it is impractical to include the corrective
action when the deviation requires investigation and research over an
extended period of time or involves the evaluation of multiple batches
(production aggregates) before the appropriate corrective action is
identified. In these cases, the comment maintained, it would be
impractical to place a copy of the corrective action taken into the
record of each affected batch (production aggregate) after the fact but
it would be sufficient to require documentation of the manufacturer's
response to each deviation in its respective batch (production
aggregate) record. The comment argued that this action would include
responses to the deviations, if immediately known, or a statement of
the need for further evaluation, or some other appropriate indication
of the status of the investigations or corrective action.
    (Response) FDA is not persuaded by this comment because it ignores
the role of production records, including records of corrective
actions, in ensuring the safety of infant formula.
    In the preamble to the 1996 proposal, FDA discussed why these
records must appear in the production aggregate production and control
record (61 FR 36154 at 36190-36191). These records have a critical role
helping the manufacturer to ensure that the infant formula is in
compliance with the CGMP requirements for infant formula and to ensure
that any deviation that has occurred during the production of the
infant formula will not adulterate or lead to adulteration of the
product. A manufacturer must not release a finished production
aggregate of infant formula until it determines that the production
aggregate meets all of its specifications, or until the documented
review of the failure to meet any of the manufacturer's specifications
finds that the failure does not result in, or could not lead to,
adulteration of the product (see Sec.  106.70(a) of the interim final
rule). A manufacturer would need to determine what, if any,
specifications are or may not be met and otherwise address a deviation
from the master manufacturing order before the production aggregate of
infant formula is released for distribution. Thus, any determination of
how to handle a deviation will occur during the time period when the
production and control record is being prepared. Once a manufacturer
has determined how to handle a deviation from specifications, any
corrective action shall be recorded and that record made part of the
production aggregate record at that time.
    Furthermore, if a deviation is noted in the production and control
record for the production aggregate, documentation of any corrective
action taken must appear in the production aggregate record to make it
complete and to ensure that the deviation was appropriately
investigated and addressed. Therefore, documentation of any corrective
action(s) taken is appropriately part of the production and control
record for the production aggregate to provide a basis for the ultimate
decision to release (or not release) the production aggregate for
distribution. Because the record of a corrective action is part of the
history of a particular production aggregate, this documentation should
not be maintained in another record or location that is not linked
directly and closely to the production of the particular production
aggregate of infant formula. In addition, the comment provided no
rationale for why FDA should use the term ``specific actions'' instead
of ``corrective actions.'' For these reasons, FDA is not revising
proposed Sec.  106.100(e)(2), proposed Sec.  106.100(e)(3)(ii), and
proposed Sec.  106.100(e)(4)(i) in response to this comment, and these
provisions are included in this interim final rule as proposed.
2. Records of the Production and In-process Control System
    (Comment 305) One comment suggested revising proposed Sec.
106.100(e)(3) by changing the term ``necessary'' to ``critical'' and
thus requiring that documentation be included where control is deemed
critical to prevent adulteration.
    (Response) FDA is not persuaded by this comment. As discussed
previously in this document in section IV.C.8, FDA is not persuaded
that the word ``critical'' enhances the clarity of the phrase
``necessary to prevent adulteration.'' Therefore, FDA is not revising
proposed Sec.  106.100(e)(3) in response to this

comment, and this provision is included in this interim final rule as
proposed.
    (Comment 306) One comment suggested that proposed Sec.
106.100(e)(4)(i) be revised to state ``any deviation from the
manufacturing order and any specific action taken to adjust or correct
a batch [production aggregate] in response to a deviation,'' and that,
as a result, proposed Sec.  106.100(e)(4)(iii) could be deleted as
redundant. (Proposed Sec.  106.100(e)(4)(iii) would require that the
batch (production aggregate) production and control record contain the
conclusions and followup, along with the identity, of the individual
qualified by training or experience who investigated a failure to meet
any standard or specification at any point, step, or stage in the
production process where control is necessary to prevent adulteration.)
    (Response) FDA declines to make the suggested revisions to Sec.
106.100(e)(4) in the interim final rule. The comment did not provide a
reasoned basis for substituting the term ``specific action'' for
``corrective action'' or for inserting the phrase ``to adjust or
correct a batch in response to a deviation'' to describe the corrective
actions taken. Further, FDA disagrees that Sec.  106.100(e)(4)(iii)
would be redundant with proposed Sec.  106.100(e)(4)(i) even if the
latter provision were revised as suggested. The scope of proposed Sec.
106.100(e)(4)(i) and proposed Sec.  106.100(e)(4)(iii) are very
different. Proposed Sec.  106.100(e)(4)(i) covers only deviations from
the master manufacturing order. (A master manufacturing order provides
the plan for manufacture of the infant formula.) In contrast, proposed
Sec.  106.100(e)(4)(iii) relates to the investigation of a failure to
meet any specification in the production process where control is
deemed necessary to prevent adulteration, a provision that extends to
the entire production process, including a deviation from the master
manufacturing order and a deviation from any part of the manufacturing
process, such as a deviation from the provisions of proposed Sec. Sec.
106.10, 106.20, 106.30 106.35 or 106.40. Accordingly, FDA is not
revising Sec.  106.100(e)(4) as requested in this comment.
3. Records on Production Aggregate (Batch) Testing
    (Comment 307) One comment objected to the stability testing record
requirements in proposed Sec.  106.100(e)(5), which would require that
the batch (production aggregate) production and control record include
records of the results of all testing performed on the batch
(production aggregate) of infant formula, including testing on the in-
process product, at the final product stage, and on finished product
throughout the shelf life of the product. The comment argued that the
requirement to include all stability test results in the individual
batch (production aggregate) records is an additional administrative
burden and can easily be avoided by requiring that shelf life testing
results be made available to the Agency upon request, either by outside
communication or through inspection. The comment stated that if a
requirement were made to store the data with the manufacturing work
order, an additional system would need to be developed to link the data
at an additional cost with no commensurate benefit to public health.
    (Response) FDA is not persuaded that requiring all stability
testing results to be included in the production aggregate production
and control record would be an unwarranted administrative burden to
formula manufacturers. FDA notes that the comment's concern was limited
to the administrative burden of maintaining stability records in the
production and control record and did not explain why stability testing
records are different from all other testing records in terms of such
burden.
    The principle underlying proposed Sec.  106.100(e)(5) is that all
testing records that relate to a specific production aggregate (batch)
must be co-located (or linked electronically) so that, should there be
an adulteration concern about a particular production aggregate, both
the manufacturer and FDA can have immediate access to all relevant
testing records for the formula in question. Also, maintaining
stability testing records in the production and control record will
help avoid duplication. This is because the final product testing that
would be required by proposed Sec.  106.91(a)(4) may also serve as the
initial (baseline) stability testing.
    The Agency acknowledges that, with the exception of initial
stability testing, all stability testing is likely to occur after the
finished infant formula has been released for distribution, and the
production and control record for a production aggregate is likely to
be established at or near the time the formula is manufactured.
However, it is not unreasonable to require stability testing records to
be co-located (for hard copy records) or electronically linked (for
electronic records) with the production aggregate production and
control record and that any records created post-distribution may
simply be added to or linked with the production and control record. As
noted, the comment did not distinguish stability testing records from
other production records that this interim final rule requires to be
maintained in the production aggregate production and control record.
Absent such distinction, it is entirely reasonable that stability
testing records be maintained with other records relating to a
particular production aggregate.
    Moreover, as discussed in section VI. Quality Control Procedures,
stability testing of finished infant formula is critical because it
evaluates whether all nutrients (both those required by Sec.  107.100
and those otherwise added by the manufacturer) are present in the
formula at the desired level throughout the formula's shelf life. A
formula that lacks one or more of these nutrients at the appropriate
level may be unable to support normal growth of the infants consuming
it as their sole source (or virtually sole source) of nutrition.
Similarly, the records of stability testing of a particular production
aggregate are an integral part of the history of the particular
production aggregate of formula and, like other production records that
supply the history of a production aggregate, these stability testing
records need to be immediately accessible to both the manufacturer and
FDA. For these reasons, FDA declines to revise Sec.  106.100(e)(5) in
response to this comment.
    (Comment 308) Another comment suggested that because the results of
stability testing should be required as a part of the good
manufacturing practice records instead of as a part of the batch
(production aggregate) production and control records, the summary of
results from the stability testing program required by proposed Sec.
106.100(e)(5)(i)(B) should be incorporated into the good manufacturing
practice records.
    (Response) FDA disagrees with this comment. As outlined in the
preceding response, records of stability testing are part of the
manufacturing history of the particular production aggregate and, as
such, are reasonably required to be maintained in the production
aggregate production and control record. The summary of such testing
required by Sec.  106.100(e)(5)(i)(B) of the interim final rule is
appropriately maintained as part of the same production and control
record. Thus, FDA is not making any revisions in response to this
comment.
    (Comment 309) One comment suggested that FDA revise both proposed
Sec.  106.100(e)(5)(i)(A), which would require a summary table
identifying the stages of the manufacturing process at which the
manufacturer conducts the nutrient analysis required under proposed

Sec.  106.91(a) for each required nutrient, and proposed Sec.
106.100(e)(5)(i)(B), which would require a summary table of the
stability testing program that would be required under proposed Sec.
106.91(b), including the nutrients tested and the testing frequency for
nutrients throughout the shelf life of the product. The comment
suggested that ``table'' should be changed to ``document'' because
``document'' implies a reference best suited to the manufacturer's
system, as opposed to a specific type of a reference, such as table.
    (Response) FDA agrees with this comment. It is reasonable to
provide formula manufacturers with flexibility to create a summary
document so long as the chosen format accurately and succinctly conveys
the data identified as appropriate in proposed Sec.  106.91(a) and
proposed Sec.  106.91(b). The summary document may, but is not required
to, be in the form of a table, if the manufacturer determines that such
format is a convenient and accurate summary document. Thus, in response
to this comment FDA is modifying both Sec.  106.100(e)(5)(i)(A) and
(e)(5)(i)(B) by changing the word ``table'' to ``document.''

C. Records of CGMP (Proposed Sec.  106.100(f))

    FDA did not receive any comments requesting modification of
proposed Sec.  106.100(f)(1) and proposed Sec.  106.100(f)(3). Thus,
these provisions are included in this interim final rule as proposed.
FDA received a comment on proposed Sec.  106.100(f)(2), which suggested
that the words ``standards'' be omitted from that provision. As
discussed previously in this document, the Agency agrees generally with
this comment and has revised several provisions in this interim final
rule, including proposed Sec.  106.100(f)(2), by deleting ``standard
or.''
1. Records on Equipment and Utensils
    (Comment 310) One comment objected to the inclusion of the ``lot
number'' in proposed Sec.  106.100(f)(4), which would require that
records be maintained, in accordance with proposed Sec.  106.30(f), on
equipment cleaning, sanitizing, and maintenance that show, among other
things, the lot number of each batch (production aggregate) of infant
formula processed between equipment startup and shutdown for cleaning,
sanitizing, and maintenance. Proposed Sec.  106.100(f)(4) also would
require the person performing and checking the cleaning, sanitizing,
and maintenance to date and sign or initial the record indicating that
the work was performed. The comment contended that the requirement to
document all lot numbers of batches (production aggregates) produced
between all equipment cleaning, sanitizing, and maintenance is an
overwhelming administrative requirement that is unnecessary on a daily
basis. The comment asserted that the records should have sufficient
detail and reference points (e.g., time, location) to allow
reconstruction of this type of information if needed, but to require it
routinely serves no purpose.
    (Response) FDA disagrees. Accurate recordkeeping on equipment
cleaning, sanitizing, and maintenance showing the date and time of such
activities will provide a means by which the manufacturer can ensure
that equipment is being cleaned and maintained regularly and that the
frequency of such cleaning is appropriate in light of the actual use of
the equipment. Moreover, records that identify the production unit
number or production aggregate number (see Sec.  106.3 of the interim
final rule) of each production unit or production aggregate of infant
formula processed between equipment startup and shutdown for cleaning,
sanitizing, and maintenance are essential in situations of equipment
contamination because such records will permit a manufacturer to
determine which production units or production aggregates of infant
formula are or may be adulterated. Thus, the requirements of Sec.
106.100(f)(4) are both reasonable and critical to the production of
safe infant formulas.
    FDA is not persuaded that Sec.  106.100(f)(4) should be modified
because other records could be used to reconstruct this information, if
needed. The most reliable and accurate way to develop this type of
information is to create an appropriate record in real time for this
specific purpose. Maintaining this type of information would be
particularly important when equipment maintenance, planned or
unplanned, might have an impact on infant formula production aggregates
produced between the previous maintenance and the time the equipment
was repaired. In such a case, it may be necessary for a firm to
investigate and identify which production aggregates were manufactured
between those time periods. These records will complement the
production aggregate production and control records and will facilitate
a manufacturer's trace back to all potentially affected production
units or production aggregates when there is an instance of an
equipment failure that might result in an adulterated product (e.g.,
microbiological contamination). Therefore, FDA is not revising proposed
Sec.  106.100(f)(4) in response to this comment, and this provision is
included in this interim final rule, with minor editorial changes, as
proposed.
2. Records on Automatic Equipment
    (Comment 311) One comment suggested, consistent with the comment's
recommendation that proposed Sec.  106.35 be deleted, the deletion of
proposed Sec.  106.100(f)(5), which relates to records on automatic
(mechanical or electronic) equipment required in accordance with
proposed Sec.  106.35(c).
    (Response) As discussed previously in this document in section V.G,
FDA does not agree that proposed Sec.  106.35 should be eliminated. As
noted in that discussion, the Agency has clarified the application of
validation to the manufacture of infant formula. Because the comment
provides no independent basis for deleting proposed Sec.
106.100(f)(5), FDA declines to eliminate the recordkeeping requirements
of proposed Sec.  106.100(f)(5) in response to this comment.
    (Comment 312) One comment suggested that proposed Sec.
106.100(f)(5)(i), which requires a list of all systems used with a
description of computer files and the inherent limitations of each
system, be revised to require a list of all systems used with a
description of computer files and the defined capabilities of each
system. The comment asserted that the range in capability of a system
is a better description than the inherent limitations of a system and
would include at least the same information.
    (Response) FDA disagrees that providing the defined capabilities of
each system would provide a better description of the system rather
than a description of the system's inherent limitations. The purpose of
proposed Sec.  106.100(f)(5)(i) is to require that the records for
automatic equipment include a sufficiently detailed description of the
system to enable the manufacturer to operate and troubleshoot the
system. The Agency disagrees that a description of the defined
capabilities of a system would include the same information as a
description of the inherent limitations of a system. A description of
the defined capabilities of a system identifies what the system is
designed to do while a description of the system's inherent limitations
identifies what the system is incapable of doing. Upon further
consideration, FDA has determined that in order for a manufacturer to
operate and troubleshoot a system, it is essential that a
manufacturer's records include a description of both the defined
capabilities and inherent limitations of

the system. Accordingly, FDA is revising Sec.  106.100(f)(5)(i) to
require ``A list of all systems used with a description of the computer
files and the defined capabilities and inherent limitations of each
system.''
    (Comment 313) One comment on proposed Sec.  106.100(f)(5)(vii)
asserted that hard copy recording should be reduced to a minimum and
attempts made to ensure that all key process results are obtained
electronically because the latest instruments automatically record to a
computer with data processing, graphing, and alarm signals produced
instantaneously. The comment claimed that back-up methods can eliminate
fears of data loss so there is now no need for burdensome recording
better suited to the last century.
    (Response) FDA agrees that technology has changed since publication
of the proposal and has made modifications to the interim final rule to
permit the use of back-up systems that may become available in the
future as well as those systems currently in use. Specifically, FDA is
revising Sec.  106.100(f)(5)(vii) to delete the reference to specific
older storage systems (e.g., diskettes) and to substitute the term
``electronic records.'' This will provide a manufacturer with the
option to use newly developed technologies, if the manufacturer chooses
to do so. Thus, Sec.  106.100(f)(5)(vii) of the interim final rule
requires ``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 electronic records, tapes, or microfilm,
designed to ensure that backup data are exact and complete, and that
they are secure from alteration, inadvertent erasures, or loss.''

D. Records on Infant Formula for Export Only (Proposed Sec.
106.100(g))

    (Comment 314) One comment requested clarification of proposed Sec.
106.100(g), which requires that the manufacturer maintain all records
pertaining to distribution of an infant formula, including records
showing that products produced for export only are exported. The
comment stated that it is reasonable to expect a manufacturer to
maintain distribution records regarding shipment of infant formula
under the manufacturer's control. However, the comment contended that
once the infant formula is in the hands of the retailer, customer,
consumer, or exporter, the manufacturer can no longer be responsible
for obtaining or keeping these records and should not retain that
responsibility after the infant formula has left its control. The
comment also stated that sometimes manufacturers ship infant formula to
a customer who, in turn, intends it only for export. Because the
manufacturer is not responsible for the actual export, the manufacturer
would have no records regarding distribution of such infant formula
after it is turned over to the exporter.
    (Response) FDA agrees that an infant formula manufacturer must
maintain distribution records regarding shipment of infant formula
under the manufacturer's control, including records of shipments to a
manufacturer's consignees. Such distribution records are routinely
maintained by manufacturers. Thus, if a consignee is a foreign
purchaser, the manufacturer would have records of shipment to such
consignee. A sale of infant formula for export only directly to a
foreign purchaser would be consistent with the requirement in section
801(e)(1)(D) of the FD&C Act (21 U.S.C. 381(e)(1)(D)) that a product
not be ``sold or offered for sale in domestic commerce,'' provided that
the product is, in fact, exported. In contrast, if a manufacturer sells
an infant formula to a distributor in the U.S., the manufacturer would
not be in compliance with section 801(e)(1)(D) of the FD&C Act because
this transaction would involve the sale (or the offer for sale) of the
infant formula in domestic commerce. FDA recognizes that, in some
cases, however, a manufacturer may transfer an infant formula to a
domestic third-party (e.g., contractor or other agent of the
manufacturer) who, on behalf of the manufacturer, exports the product
to a foreign consignee. This latter transaction would not be considered
a ``sale'' of the infant formula in domestic commerce for the purposes
of section 801(e)(1)(D) of the FD&C Act because there is no transfer of
ownership to the third-party acting on behalf of the manufacturer. In
such situation, FDA expects that the manufacturer would have access to
the records of export of such third-party. Therefore, where the
manufacturer ships its product to a foreign consignee, either directly
or through a third-party who ships such product to a foreign consignee,
the manufacturer would have the necessary access to distribution
records (e.g., bill of lading) showing that the infant formula produced
for export only is actually exported. The distribution records are
required under section 412(g) of the FD&C Act and are required by
current Sec.  106.100(l) to be available for inspection. FDA notes that
these and other records may also be required under 21 CFR 1.101(b)(4)
for foods, in general, that are for export only.
    For the foregoing reasons, FDA is only making minor editorial
changes to Sec.  106.100(g).
    In the proposed rule, FDA expressed concerns about infant formulas
produced for export only that are diverted and sold in the United
States (61 FR 36154 at 36194). Proposed Sec.  106.100(g) was intended,
in part, to be a means to verify that the infant formula was not in
fact sold or offered for sale in domestic commerce. Id. A manufacturer
of an infant formula for export only has a responsibility under section
801(e)(1)(D) of the FD&C Act and section 412(b)(2) of the FD&C Act to
ensure that it or any third-party acting on its behalf exports the
infant formula for export only and does not divert it for sale in
domestic commerce. As noted previously in this document, under section
801(e) of the FD&C Act, an infant formula for export only is deemed not
to be adulterated or misbranded if the formula satisfies the criteria
in section 801(e) of the FD&C Act, including that it is not sold or
offered for sale in domestic commerce. In order to move such a product
lawfully in interstate commerce, the manufacturer must take the
necessary steps to ensure that the product complies with section 801(e)
of the FD&C Act. See United States v. Parfait Powder Puff Co., 163 F.2d
1008, 1010 (7th Cir. 1947) (explaining that ``one who owes a certain
duty to the public and entrusts its performance to another, whether it
be an independent contractor or agent, becomes responsible criminally
for the failure of the person to whom he has delegated the obligation
to comply with the law, if the nonperformance of such duty is a
crime''). Further, a manufacturer of infant formula for export only,
which formula is otherwise adulterated or misbranded under U.S. law,
has an obligation under section 412 of the FD&C Act to establish
adequate controls under CGMP respecting the distribution of such
product to ensure that adulterated product is not sold or offered for
sale in domestic commerce.
    Section 412(d) of the FD&C Act requires a formula manufacturer to
make certain submissions that provide assurances that the firm's
formula is not adulterated. FDA is not requiring, under the
requirements in Sec.  106.120 of the interim final rule for new infant
formula submissions, that a manufacturer of infant formula for export
only submit the same information that would be required for a formula
intended or offered for sale in domestic commerce. Instead, to meet the
requirements in

sections 412(d)(1)(C) and (D) of the FD&C Act and Sec.  106.120 of the
interim final rule, such a manufacturer may provide assurances that
include, among other commitments, that the infant formula will not be
sold or offered for sale in domestic commerce, consistent with section
801(e) of the FD&C Act. In addition, to ensure that a manufacturer
takes the necessary precautions to prevent an infant formula it
distributes for export only from being diverted for sale in domestic
commerce, FDA is requiring in this interim final rule, as part of the
submission requirements in Sec.  106.120(c) of the interim final rule,
that a manufacturer of infant formula for export only certify that it
has adequate controls in place to ensure its formula for export only is
actually exported (see discussion in section X.C.3 for Sec.  106.120(c)
of the interim final rule). In making this certification, the
manufacturer is assuring that the product will not be sold or offered
for sale in domestic commerce and thereby meets the requirements of the
FD&C Act under sections 412(d)(1)(C) and (D) that, if not met, would
result in the formula being deemed adulterated under sections 412(a)(2)
and (3) of the FD&C Act.

E. Means of Recordkeeping (Sec.  106.100(m))

    (Comment 315) One comment recommended that the final regulation
reflect the acceptability of electronic recordkeeping.
    (Response) FDA agrees that it may be appropriate to use electronic
recordkeeping to meet the requirements of Sec.  106.100, provided that
the records are maintained in accordance with part 11 (21 CFR part 11).
Part 11 applies to any electronic records that are maintained to comply
with the requirements of this interim final rule. The Agency advises
that the use of electronic records is voluntary and thus, a paper
record system may be used to comply with these recordkeeping
requirements. In response to this comment, FDA is revising Sec.
106.100(m) to state that records required under part 106 may be
retained as original records, as true copies of the original records in
a form such as photocopies, microfilm, microfiche, or other accurate
reproductions of the original records, or as electronic records. In
addition, FDA is modifying Sec.  106.100(m) to require all electronic
records maintain under part 106 to comply with part 11.
    The requirements for electronic records extend to electronic
signatures. FDA has issued final guidance for industry on this topic.
The guidance entitled ``Part 11, Electronic Records; Electronic
Signatures Scope and Application'' sets out the Agency's enforcement
policies with respect to certain aspects of part 11. The guidance is
available at http://www.fda.gov/RegulatoryInformation/Guidances/ucm125067.htm. This guidance applies to any electronic record,
including electronic signatures, established or maintained to meet a
requirement in this interim final rule.

F. Records of Quality Factors (Sec.  106.100(p) and (q))

    For consistency with other records requirements, FDA is adding two
new provisions to Sec.  106.100 of the interim final rule to clarify
the requirements for making and retaining records that demonstrate that
an infant formula meets the quality factor requirements. All of the
records requirements for part 106 are located in subpart F. Therefore,
for comprehensiveness and clarity, FDA is adding language to Sec.
106.100 in the interim final rule to include the recordkeeping
requirements for quality factors.
    As is discussed in section VIII.I, the interim final rule contains
the requirement that an infant formula manufacturer make and retain
records demonstrating that such formula meets the quality factors
requirements. Section VIII.I also explains that, although both
``eligible'' and non-eligible formulas will be required to meet the
quality factors of normal physical growth and sufficient biological
quality of protein, ``eligible infant formulas'' will be able to use
separate established criteria to demonstrate compliance with those
quality factors. As such, these new provisions in subpart F describe
the separate quality factor records requirements for eligible formulas
and non-eligible formulas. For a formula that is not an eligible
formula, the manufacturer of the formula must make and retain records
that demonstrate compliance with the requirements in Sec.  106.96(b)
and (f) of the interim final rule, or, as applicable, an exemption to
either provision. An eligible formula manufacturer must make and retain
records that demonstrate compliance with the requirements in Sec.
106.96(i)(1) and (i)(2) of the interim final rule.

G. Adulteration as a Consequence of the Failure To Keep Records (Sec.
106.100(r))

    For clarity, FDA is also adding a paragraph to Sec.  106.100 in the
interim final rule that discusses when an infant formula will be
considered adulterated for the failure to make or retain a record.
    As noted, the records requirements in part 106 are located in
subpart F. However, despite the fact that these records provisions are
located in subpart F, many of these records are considered to be a
current good manufacturing practice, quality control procedure, or
quality factor requirement. For example, Sec.  106.100(e)(3) of the
interim final rule requires records documenting the monitoring at any
point, step, or stage in the manufacturer's production process where
control is deemed necessary to prevent adulteration. Such monitoring is
a part of good manufacturing practices. Thus, although the substance of
the recordkeeping requirement to make and retain records of this
practice is located in subpart F, Sec.  106.100(e)(3) of the interim
final rule is also a part of current good manufacturing practices.
    Because some of the requirements in subpart F are a part of the
current good manufacturing practices, quality control procedures, and
quality factor requirements, the failure to follow some of the
requirements in subpart F will necessarily adulterate the infant
formula. The failure to follow any CGMP or quality control requirement
will adulterate the formula under section 412(a)(3) of the FD&C Act.
Likewise, the failure to follow any quality factor requirement will
adulterate the formula under section 412(a)(2) of the FD&C Act.

X. Subpart G--Registration, Submission, and Notification Requirements

    In the 1996 proposed rule, FDA proposed a new subpart G to
establish requirements for registration by an infant formula
manufacturer (implementing section 412(c)(1)(A) of the FD&C Act),
submission of information relating to a new infant formula
(implementing section 412(d) of the FD&C Act), and notification
relating to any adulterated or misbranded infant formula that has left
the control of a manufacturer (implementing section 412(e) of the FD&C
Act.) The 2003 reopening requested comments on all aspects of the 1996
proposal, including proposed Subpart G.
    FDA received comments on a number of the provisions in proposed
subpart G. The Agency's responses are set out in this document.

A. General Comments

    Several comments stated that the premarket notification
requirements of section 412(c) and (d) of the FD&C Act do not
constitute a premarket approval process for infant formula and cited
legislative history in support of their assertion.

    (Comment 316) One comment stated that FDA's role in the premarket
notification process was perceived by Congress as comprising the task
of confirming that the required [nutrient] specifications are met for
each new or significantly modified formula.
    (Response) FDA disagrees with the comment to the extent that it
suggests that FDA's role in the premarket notification process is
limited to confirming that the FD&C Act's nutrient specifications are
met. In fact, through the premarket notification process in section 412
of the FD&C Act, Congress assigned FDA a comprehensive role in
evaluating new infant formulas. As noted in the 1996 proposal, the FD&C
Act requires that the manufacturer of a new infant formula submit a
variety of information on the new infant formula, including information
on its quantitative composition, on any reformulation, on any changes
in processing, assurances that quality factor requirements have been
met, assurances that the nutrient requirements have been met, and
assurances that the manufacturing adhere to CGMP and quality control
procedures. All of this information is reviewed by the Agency to ensure
that the infant formula will be a safe product that adheres to all
applicable laws and regulations.
    (Comment 317) Another comment asserted that, over the years, the
practices and procedures FDA has followed in reviewing notifications
under section 412 of the FD&C Act have consistently taken on more and
more of the trappings of premarket approval systems quite different
from the limited, precise review function contemplated in the statutory
scheme.
    (Response) As explained in the previous response, FDA disagrees
that the Agency's review role under section 412 of the FD&C Act is a
narrow one. In addition, the comment did not provide any underlying
details to explain its assertion that FDA's review procedures have
``taken on the trappings of premarket approval systems.''
    Accordingly, the Agency is making no changes to the rule in
response to Comments 316 and 317.
    (Comment 318) One comment requested that the Agency establish and
make public a well-defined, transparent, and practical process for the
receipt, review, and disposition of various infant formula submissions
from industry. The comment suggested that the process include review
time lines, the definition of the review process, the identification of
reviewers, and a response and dialogue process, and asserted that such
process definition is necessary for industry planning and
implementation of infant formula advancements in a mutually cooperative
manner.
    (Response) FDA disagrees in part with this comment. The interim
final rule provides a well-defined, transparent, and practical process
for the receipt and review of the infant formula submissions required
by section 412 of the FD&C Act. The interim final rule clearly
identifies the information that must be provided to FDA in the various
submissions, the form in which it is to be submitted, and where the
information is to be submitted. Under the FD&C Act, a manufacturer must
make a submission to FDA at least 90 days before marketing a new infant
formula.
    FDA does not agree that certain matters should be made available to
the public, as suggested by the comment. In particular, review time
lines, a description of the review process, and the identification of
Agency reviewers are all internal administrative management items and
are not relevant to a manufacturer's obligations or responsibilities
under the FD&C Act. Indeed, the comment itself did not explain why
formula manufacturers need such information. Accordingly, the interim
final rule does not commit FDA to disclosing these types of details.

B. New Infant Formula Registration (Proposed Sec.  106.110)

    In 1996, FDA proposed to establish requirements to implement
section 412(c)(1)(A) of the FD&C Act. Specifically, FDA proposed in
Sec.  106.110 that, before a new infant formula may be introduced or
delivered for introduction into interstate commerce, the manufacturer
of such formula must register with FDA and provide the name of such
formula, the name of the manufacturer, the manufacturer's place of
business, and all establishments at which the manufacturer intends to
manufacture such formula.
    The Agency responds in this document to the comments received on
proposed Sec.  106.110.
    (Comment 319) One comment suggested that FDA revise proposed Sec.
106.110 on new infant formula registration to require that
manufacturers of infant formula for export register with FDA. The
comment suggested revising Sec.  106.110 to include the requirement
that infant formula products for export only comply with section 801(e)
of the FD&C Act and deleting the requirement in Sec.  106.120(c), a
revision that would, the comment asserted, reduce the time and expense
for preparing and reviewing submissions for infant formula intended for
export.
    (Response) FDA agrees that the interim final rule should require a
manufacturer of an infant formula product intended for export only to
register with FDA. Section 412(c)(1)(A) of the FD&C Act requires that
no person shall introduce or deliver for introduction into interstate
commerce any new infant formula unless such person has registered with
the Secretary (and by delegation, FDA). The act of exporting infant
formula necessarily requires the introduction or delivery for
introduction into interstate commerce of the formula. Infant formula
manufactured for export only may nonetheless be a ``new infant
formula'' as defined in Sec.  106.3 of the interim final rule.
Therefore, FDA is revising Sec.  106.110(a) in the interim final rule
to clarify that a manufacturer who produces formula for export only is
required to register with FDA. The Agency is also revising Sec.
106.110(a) to update the contact information for FDA's Center for Food
Safety and Applied Nutrition. Thus, Sec.  106.110(a) of the interim
final rule states ``Before a new infant formula may be introduced or
delivered for introduction into interstate commerce, including a new
infant formula for export only, the manufacturer of the formula shall
register with the Food and Drug Administration, Center for Food Safety
and Applied Nutrition, Office of Nutrition, Labeling, and Dietary
Supplements, Infant Formula and Medical Foods Staff (HSF-850), 5100
Paint Branch Pkwy., College Park, MD 20740-3835.''
    The Agency disagrees that proposed Sec.  106.110 should be revised
to require that infant formula products intended for export comply with
section 801(e) of the FD&C Act and that proposed Sec.  106.120(c) be
deleted for the reasons the comment provided. A manufacturer of an
infant formula for export only must still provide a submission under
sections 412(c)(1)(B) and (d)(1) of the FD&C Act. Section 412(c)(1)(B)
of the FD&C Act requires that no person shall introduce or deliver for
introduction into interstate commerce any new infant formula unless
such person has at least 90 days before marketing such new infant
formula made the submission required under the FD&C Act. The failure to
provide notice under section 412(c) of the FD&C Act, including the
submission in section 412(d)(1) of the FD&C Act, is a prohibited act
under section 301(s) of the FD&C Act (21 U.S.C. 331(s)). However, as is
explained in response to Comment 328, FDA is revising Sec.  106.120(c)
in the interim final

rule to clarify the assurances that must be provided for infant formula
for export only.
    (Comment 320) One comment suggested that proposed Sec.
106.110(b)(4), which would require that the new infant formula
registration include all establishments at which the manufacturer
intends to manufacture such new infant formula, be revised to require
the name and addresses of all establishments at which the manufacturer
intends to manufacture such new infant formula.
    (Response) FDA agrees with this comment. The name and address of
the establishments is a necessary component of the registration and
will allow the Agency to identify and locate each establishment; only
if FDA can locate an establishment can the Agency inspect such firms
and otherwise carry out its regulatory responsibilities. Therefore,
Sec.  106.110(b)(4) of the interim final rule requires that the new
infant formula registration include the name and street address of each
establishment at which the manufacturer intends to manufacture a new
infant formula.

C. New Infant Formula Notifications (Proposed Sec.  106.120)

    In 1996, FDA proposed to establish requirements to implement
section 412(c)(1)(B) and 412(d)(1) of the FD&C Act. Specifically, FDA
proposed in Sec.  106.120 that at least 90 days before the interstate
distribution of a new infant formula, a manufacturer submit certain
information to FDA pertaining to the new infant formula.
    FDA received a number of comments on proposed Sec.  106.120 and
responds in this document to those comments.
1. Form of Submission (Proposed Sec.  106.120(a))
    The proposed rule, Sec.  106.120(a), would have required that an
original and two copies of a new infant formula submission be provided
to FDA. As discussed previously in this document, in response to a
comment, Sec.  106.100(m) of the interim final rule permits a
manufacturer to maintain records as original paper records, as true
copies of the originals (e.g., microfilm), or as electronic records.
Such electronic records are required to conform to 21 CFR Part 11.
Consistent with this revision, FDA is, on its own initiative, revising
Sec.  106.120(a) in the interim final rule to permit new infant formula
submissions to be submitted electronically and, in such case, to
require only a single copy of such electronic submission. Thus, Sec.
106.120(a) of the interim final rule states, ``At least 90 days before
a new infant formula is introduced or delivered for introduction into
interstate commerce, a manufacturer 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 paper copies of the notice of its
intent to do so shall be submitted, unless the notice is submitted in
conformance with part 11 of this chapter, in which case, a single copy
shall be sufficient.''
2. Contents of a New Infant Formula Submission (Proposed Sec.
106.120(b))
    Proposed Sec.  106.120(b) would have established the required
contents of a new infant formula submission. FDA received comments on a
number of the provisions of proposed Sec.  106.120(b), and responds in
this section.
    a. Quantitative formulation (Proposed Sec.  106.120(b)(3)).
    (Comment 321) One comment questioned the requirement in proposed
Sec.  106.120(b)(3) that the quantitative formulation of the new infant
formula be submitted in units per volume for liquid formulas. The
comment asserted that formulations are routinely listed and have
traditionally been submitted to the Agency in units per weight of
liquid. The comment also requested clarification of the volume units to
use in the quantitative formulation and whether the information should
be provided on an ``as sold'' or ``as fed'' basis in the submission.
    (Response) The Agency has examined previously received infant
formula submissions and determined that the formulations of liquid
formulas have been provided to the Agency in either units per weight
(e.g., milligrams/kilogram) or in units per volume (e.g., milligrams/
liter). Accordingly, the interim final rule, at Sec.  106.120(b)(3),
permits a manufacturer to provide the quantitative formulation of a new
infant formula either in units per weight or units per volume, and on
an ``as sold'' or ``as fed'' basis, provided that the manufacturer
specifies whether the quantitative formulation is on an ``as sold'' or
``as fed'' basis. For a powdered infant formula, the submission must
also specify the weight of powder to be reconstituted in a specific
volume of water (e.g., grams (g) of powder per fluid (fl) ounce (oz) of
water).
    (Comment 322) One comment requested clarification on whether FDA
requires a table of nutrients as well as a table of ingredients as part
of the quantitative formulation.
    (Response) The interim final rule does not require a manufacturer
to submit a table reflecting the amount of various nutrients in an
infant formula formulation as part of the requirement to provide the
quantitative formulation. FDA is taking this opportunity to clarify
that the ``quantitative formulation'' required by section 412(d)(1)(A)
and (d)(3) of the FD&C Act is a list of all ingredients (including
individual ingredients and premixes of two or more ingredients) in a
product and the amount by weight of each ingredient in a set volume or
weight of the formula. For example, several ingredients in an infant
formula formulation may contain calcium. Thus, the quantitative
formulation would identify each individual ingredient (e.g., calcium
phosphate, calcium carbonate, calcium hydroxide) and the amount (by
weight or volume) of each ingredient. For mineral salts, the state of
hydration must be provided because the amount of water contained in the
salt affects the amount of mineral (e.g. calcium) provided. For
vitamins, the source of the vitamin (e.g., vitamin A palmitate or
vitamin A acetate) must be provided because the proportion of vitamin
differs with each source.
    If a nutrient is added to the formulation as a part of a premix,
the form of the nutrient and the amount the nutrient must be provided
(listed) as part of the premix information.
    Not all sources of nutrients may be readily apparent in
quantitative formulations, as some nutrients may be endogenous to
certain ingredients (e.g., calcium and phosphorous in condensed skim
milk). In such a case, the identity and amount of the ingredient (e.g.,
the condensed skim milk) is required to be listed in the quantitative
formulation--the amounts of endogenous nutrients (e.g., the calcium and
phosphorus contained in the condensed skim milk) would also need to be
provided, and their listing is analogous to the listing requirement for
premixes.
    Although not required by the interim final rule, including a
separate table of nutrients per 100 kcal in the submission will help to
expedite FDA's review of the new infant formula submission.
    FDA notes that under Sec.  106.130 of the interim final rule, a
manufacturer is required to provide in the verification submission for
a new infant formula the level of all nutrients contained in the
formula product that reflect the analysis of the product at the
finished product stage.
    b. Description of a change in processing (Proposed Sec.
106.120(b)(4)).
    (Comment 323) One comment objected to the requirement of proposed
Sec.  106.120(b)(4) that the description of any change in processing of
the infant formula identify the specific change and include side-by-
side, detailed schematic

diagrams comparing the new processing to the previous processing
(including processing times and temperatures). The comment asserted
that, to date, a narrative description of the change has been
acceptable and that preparing side-by-side, detailed schematic diagrams
of current and new systems would require substantial amounts of
additional administrative support, and no deficiencies in the narrative
description have been identified.
    (Response) FDA disagrees with this comment. The Agency regards the
two elements in proposed Sec.  106.120(b)(4) (narrative description of
change and side-by-side diagrams) as complementary parts that will
ensure that the Agency receives a complete picture of the proposed
processing change(s). A narrative can provide a succinct means of
describing the specific parameters of the change; however, it is not
always apparent where the change fits into the overall processing
operation, and detailed side-by-side diagrams of the current and new
processing systems provide an efficient way to present the entire
picture of the infant formula production and draw attention to the
specific change or changes. These diagrams assist the Agency in
understanding the manufacturer's processing methods, the
interrelationship of various parts of the manufacturing process, and
the sequence of production events for an infant formula. At least some
infant formula manufacturers understand the value of these comparative
diagrams because they are routinely included in their infant formula
submissions to complement the narrative description of a processing
change. Because manufacturers must update their schematic processing
diagrams as part of their CGMP procedures, it seems unlikely that
requiring comparative diagrams in new infant formula submissions will
be an undue burden. For these reasons, FDA is not persuaded to revise
proposed Sec.  106.120(b)(4) in response to these comments. Section
106.120(b)(4) is included in this interim final rule as proposed, with
the exception of minor editorial changes.
    c. Assurance for quality factors (Proposed Sec.  106.120(b)(5)).
    In 1996, FDA proposed to implement section 412(d)(1)(C) of the FD&C
Act through proposed Sec.  106.120(b)(5). Proposed Sec.  106.120(b)(5)
would have required a new infant formula submission to include
assurances that the infant formula would not be marketed unless the
formula met the quality factor requirements of section 412(b)(1) of the
FD&C Act and the nutrient content requirements of section 412(i) of the
FD&C Act. Proposed Sec.  106.120(b)(5)(i) provided that the assurances
relating to quality factor requirements would be satisfied by a
submission complying with proposed Sec.  106.121, and proposed Sec.
106.120(b)(5)(ii) provided that assurances relating to nutrient content
would be satisfied by a statement that the formula would not be
marketed unless it met the nutrient requirements of Sec.  107.100, as
demonstrated by required quality control testing.
    FDA received no comments on proposed Sec.  106.120(b)(5) that are
not addressed elsewhere in the interim final rule.
    d. Assurance for processing infant formulas (Proposed Sec.
106.120(b)(6)).
    The 1996 proposal (proposed Sec.  106.120(b)(6)) would have
required that the new infant formula submission include assurance that
the processing of the infant formula complies with section 412(b)(2) of
the FD&C Act. Proposed Sec.  106.120(b)(6)(ii) would have required that
the submission include the basis on which each ingredient meets the
requirements of Sec.  106.40(a) and that any claim that an ingredient
is GRAS be supported by citation to the Agency's regulations or by an
explanation of the basis for the general recognition of safety of the
ingredient in infant formula. The proposed rule would have required
that such explanation include a list of published studies and a copy of
those publications that provide the basis for the general recognition
of safety for the use of the ingredient in infant formula.
    FDA received several comments on proposed Sec.  106.120(b)(6)(ii)
and responds to those comments directly below.
    (Comment 324) One comment requested that FDA delete proposed Sec.
106.120(b)(6)(ii), challenging FDA's legal interpretation that this
information could be required as a part of the new infant formula
submission. The comment asserted that in promulgating the Infant
Formula Act, Congress intended that the law be used to ensure that the
manufacturer produce formulas that meet the Infant Formula Act nutrient
composition requirements and that are not contaminated with substances
or organisms that might adulterate the product.
    (Response) FDA disagrees with this comment. The authority for the
requirement in proposed Sec.  106.120(b)(6)(ii) is derived from section
412(d)(1)(D) of the FD&C Act. The submission requirement under section
412(d)(1)(D) of the FD&C Act requires infant formula manufacturers to
provide assurances that the formula complies with section 412(b)(2) of
the FD&C Act. The FD&C Act is silent as to the specific assurances that
must be made to demonstrate that the formula is processed in accordance
with section 412(b)(2) of the FD&C Act. Because the FD&C Act is silent,
the Agency may issue a regulation to fill any gaps in the statutory
requirement to provide assurances that an infant formula is processed
in accordance with section 412(b)(2) of the FD&C Act so long as the
regulation is not ``arbitrary, capricious, or manifestly contrary to
statute.'' See Chevron, 467 U.S. at 844.
    Section 412(b)(2) of the FD&C Act requires FDA to issue regulations
to establish good manufacturing practices and quality control
procedures that the Secretary (and by delegation, FDA) determines are
necessary to assure that the formula provides nutrients in accordance
with section 412(i) of the FD&C Act and is manufactured in a manner
designed to prevent adulteration of the formula.
    Compliance with proposed Sec.  106.120(b)(6)(ii) will provide
assurance that an infant formula is manufactured in a manner designed
to prevent adulteration. As noted previously in this document, under
the CGMP requirement in Sec.  106.40(a) of the interim final rule, the
only substances that may be used in infant formula are those that are
GRAS for such use, are used in accordance with a food additive
regulation, or are authorized by a prior sanction. The failure to use a
lawful ingredient in the manufacture of an infant formula would
adulterate such formula. To provide adequate assurance that this CGMP
requirement has been met, FDA is including a requirement that a new
infant formula submission include the basis on which each ingredient
satisfies the requirements of Sec.  106.40(a) of the interim final
rule.
    Infant formula manufacturers may add ingredients to infant formula
that are not ``nutrients'' as defined in this interim final rule. In
fact, many infant formulas on the market today contain ingredients that
are not required by section 412(i) of the FD&C Act, such as DHA, ARA,
and microorganisms referred to as ``probiotics.'' In circumstances in
which the manufacturer has determined that an ingredient is GRAS for
use in infant formula, there is no requirement under the FD&C Act that
FDA review such ingredient prior to its use in infant formula and
before the formula is marketed for use by infants. For certain
ingredients (e.g., oligosaccharides, oils containing long chain
polyunsaturated fatty acids, or intentionally added microorganisms),
identification of the

ingredient and the supplier is necessary in order for FDA to determine
whether the manufacturer is using the ingredient that has gone through
the food additive petition or GRAS notification process.
    FDA considers the provision in proposed Sec.  106.120(b)(6)(ii) to
be important in ensuring public health protection to this particularly
vulnerable population. The submission of the information required under
Sec.  106.120(b)(6)(ii) of the interim final rule will provide FDA with
the information it needs to ensure that a manufacturer has considered
the basis for why each ingredient used in its infant formula is lawful
prior to using an ingredient in the manufacture of infant formula. By
identifying the basis on which each ingredient is believed to lawful,
assurances are provided under section 412(d)(1)(D) of the FD&C Act that
the use of each ingredient is safe and suitable under the applicable
food safety provisions of the FD&C Act, as required by Sec.  106.40(a)
of the interim final rule. Therefore, FDA is not removing Sec.
106.120(b)(6)(ii) in response to this comment, and Sec.
106.120(b)(6)(ii) is included in this interim final rule as proposed.
    (Comment 325) One comment objected to this provision arguing that
Congress did not intend to give FDA premarket approval authority over
infant formula or, in this case, over food ingredients employed in
formula. The comment further asserted that 21 CFR 170.30 does not
mandate that the information the manufacturer is relying upon be
submitted to the Agency or be formally acknowledged or listed as GRAS.
    (Response) As is explained previously in this document, Congress
gave FDA the authority to establish regulations to assure that formula
is manufactured in a manner designed to prevent its adulteration, and
also gave FDA the authority to require that manufacturers provide
assurance that the formula is manufactured in such a manner. To the
extent that the comment asserts that proposed Sec.  106.120(b)(6)(ii)
establishes premarket approval authority for infant formula or its
ingredients, FDA disagrees. Proposed Sec.  106.120(b)(6)(ii) would
simply require that the manufacturer provide the basis for why each
ingredient it uses in its infant formula is safe under the FD&C Act.
The review of ingredient safety under section 409 of the FD&C Act is
separate and distinct from the responsibility for a manufacturer, as
part of CGMP, to ensure that the formula satisfies the requirements
designed to prevent the use of an unlawful ingredient in infant
formula. Therefore, FDA is making no changes to Sec.  106.120(b)(6)(ii)
in the interim final rule in response to this comment.
    (Comment 326) One comment stated that in many or most cases,
manufacturers will, in the interest of reducing regulatory
uncertainties, find it in their own self-interest to submit such
information required under proposed Sec.  106.120(b)(6)(ii); however,
such submissions should remain voluntary. Therefore, the comment
concluded, the manufacturer should be able to market the infant formula
without submitting this information, because it is the manufacturer's
responsibility to ensure the safety and suitability of its individual
infant formula products.
    (Response) As discussed previously in this document, FDA disagrees
that proposed Sec.  106.120(b)(6)(ii) should be removed from the
interim final rule, and thus, does not believe that the provisions in
proposed Sec.  106.120(b)(6)(ii) should be voluntary. Additionally, FDA
notes that ensuring that the ingredients used to produce an infant
formula are lawful under the separate applicable statutory and
regulatory requirements of the FD&C Act is still the responsibility of
the infant formula manufacturer. Nothing in this interim final rule
relieves a manufacturer of its obligations to evaluate the safety of
the ingredients in its infant formula products and to comply with other
substantive provisions of the FD&C Act relating to the safety of
ingredients in infant formula.
    (Comment 327) Several comments requested that proposed Sec.
106.120(b)(6)(ii) be revised to apply only to ``newly added''
ingredients and not to ingredients already found in infant formula. The
comments asserted that absent this change, information in infant
formula submissions would be redundant and that this information is
unnecessary for ingredients previously used and submitted by a
manufacturer.
    (Response) FDA disagrees with this comment. Only substances that
are GRAS for use in infant formula, used in accordance with a food
additive regulation, or authorized by a prior sanction may be used in
infant formula. FDA notes that it may be appropriate in certain
situations for a formula manufacturer to reference a previous
submission in order to provide the basis that an ingredient in the
formula satisfies Sec.  106.40(a) of the interim final rule.
3. Products for Export Only (Proposed Sec.  106.120(c))
    Proposed Sec.  106.120(c) would have required that for products
intended for export only, a new infant formula submission include, in
lieu of the information required under proposed Sec.  106.120(b), a
statement that the infant formula complies with section 801(e) of the
FD&C Act (i.e., that the 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).
    (Comment 328) One comment objected to proposed Sec.  106.120(c)
asserting that is it redundant with section 801(e) of the FD&C Act.
    (Response) FDA disagrees that proposed Sec.  106.120(c) is
redundant with section 801(e) of the FD&C Act. Proposed Sec.
106.120(c) would permit a manufacturer of new infant formula for export
only to submit, in lieu of the information required under Sec.
106.120(b), 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. A manufacturer of a new infant formula, including a new
infant formula for export only, is required by section 412(c)(1)(B) of
the FD&C Act to make a submission to FDA 90 days prior to going to
market. The failure to provide the notice required by section 412(c) of
the FD&C Act (which includes a submission to FDA required by section
412(d) of the FD&C Act) is a prohibited act under section 301(s) of the
FD&C Act (21 U.S.C. 321(s)). Section 412(d)(1) of the FD&C Act requires
all persons who introduce a new infant formula, or deliver such formula
for introduction into interstate commerce, to make a submission. Such
persons include those who manufacture a new infant formula for export
only; although such formula is exported, the formula is still
introduced or delivered for introduction into ``interstate commerce,''
as such term is defined in section 201(b) of the FD&C Act (21 U.S.C.
321(b)). There is no exception for an infant formula for export only in
either section 412 or section 801 of the FD&C Act to the submission
requirements of section 412 of the FD&C Act. Thus, a manufacturer that
produces an infant formula for export only is required to make a
submission under section 412(c) of the FD&C Act. Consequently, FDA is
not removing from the interim final rule the

submission requirement for these formulas.
    However, FDA is revising Sec.  106.120(c) in the interim final rule
to clarify the assurances that must be provided under section 412(d) of
the FD&C Act for a new infant formula for export only.
    Proposed Sec.  106.120(c) would allow a manufacturer of a new
infant formula for export only to make a submission to FDA that
includes a statement that the formula meets the specifications of the
foreign purchaser, does not conflict with the laws of the foreign
country to which it is intended for export, is labeled on the outside
of the package that it is intended for export only, and that it will
not be sold in domestic commerce.
    A product intended for export shall not be deemed to be adulterated
or misbranded under the provisions of the FD&C Act if such product
satisfies the criteria in section 801(e) of the FD&C Act. Thus, an
infant formula for export only would not need to show that its formula
meets those requirements of section 412 of the FD&C Act that, if not
met, would cause the product to be adulterated, provided that the
manufacturer shows that the formula meets the requirements in section
801(e) of the FD&C Act. This fact means that the submission of a
manufacturer of a new infant formula intended for export could differ
from the submission of a manufacturer of a new infant formula that is
to be sold in domestic commerce, specifically with respect to the
requirements of section 412(d)(1)(C) of the FD&C Act (quality factor
and nutrient requirements) and section 412(d)(1)(D) of the FD&C Act
(CGMP and quality control requirements), both of which establish
conditions under which a formula would be adulterated under section
412(a) of the FD&C Act. In lieu of providing assurances that the
processing of the formula complies with applicable quality factor,
nutrient, and CGMP requirements under section 412(d)(1)(C) and
(d)(1)(D) of the FD&C Act, a manufacturer of an infant formula for
export only would notify FDA in its submission that its formula
satisfies the criteria in section 801(e) of the FD&C Act.
    Importantly, however, the submission requirements in sections
412(d)(1)(A) and (d)(1)(B) of the FD&C Act do not relate to
adulteration: Section 412(d)(1)(A) of the FD&C Act requires a
submission that includes the quantitative formulation of the formula
and section 412(d)(1)(B) of the FD&C Act requires a description of any
reformulation or change in the processing of the formula. The proposed
rule would not have required a manufacturer of a new infant formula for
export only to submit the quantitative formulation of the new infant
formula or a description of any reformulation or change in the
processing of the formula.
    Because proposed Sec.  106.120(c) would allow a manufacturer of a
new infant formula for export only to make an alternate submission to
fulfill all of the submission requirements, including the requirements
not specifically related to adulteration of the infant formula, FDA is
revising Sec.  106.120(c) to permit a manufacturer of a new infant
formula for export only to make an alternative submission to satisfy
only those requirements of section 412(d)(1) of the FD&C Act that are
related to adulteration. Thus, under the interim final rule, a
manufacturer of a new infant formula for export only is required, as it
would be for an infant formula for domestic commerce, to submit the
quantitative formulation of the formula and a description of any
reformulation or change in the processing of such formula. By providing
such information, the manufacturer of a new infant formula for export
only will be complying with the submission requirement in section
412(d)(1) of the FD&C Act in a way that is consistent with the
requirements in section 801(e) of the FD&C Act. Additionally, as
explained previously in this document, FDA is revising proposed Sec.
106.120(c) to require that, as a condition of making the alternate
submission under Sec.  106.120(c), a manufacturer of a new infant
formula for export only certify that the manufacturer has adequate
controls in place to ensure that such formula is actually exported.
    (Comment 329) Several comments claimed that manufacturers of infant
formulas for export only should not be required to make the submission
under proposed Sec.  106.120(c) 90 days before marketing, asserting
that there may be situations in which 90 days advance notice could
cause hardship to a manufacturer. One comment proposed that a
manufacturer could notify FDA of its intent to export infant formula
prior to commercial distribution, arguing that this process should not
cause FDA hardship because the relative simplicity of the export
notification and the brevity of the review typically required.
    (Response) As explained in response to the previous comment, every
manufacturer of a new infant formula, including a new infant formula
for export only, is required by section 412(c)(1)(B) of the FD&C Act to
make a submission to FDA 90 days prior to going to market. Thus, FDA is
making no changes to Sec.  106.120(c) in response to this comment.
    (Comment 330) One comment suggested that proposed Sec.  106.120(c)
should be revised to state ``For products for export only and in
compliance with Section 801(e) of the FD&C Act, the information under
paragraph (b) of this section is not required and need not be
submitted.'' The comment asserted that FDA's proposed requirements
under proposed Sec.  106.120(c) are adequately covered under the FDA
Export Reform Enhancement Act and its implementing regulations (21 CFR
part 1).
    (Response) FDA disagrees with this comment. The requirements in
this interim final rule are separate and distinct from those issued
under other authorities related to requirements in 21 CFR part 1.
Section 106.120(c) of the interim final rule specifies what must be
included in a submission required under section 412(d)(1) of the FD&C
Act for a new infant formula intended for export only. As explained
previously in this document, this submission is required for all new
infant formulas, including a new infant formula for export only. The
requirements in 21 CFR Part 1, Subpart E, do not implement section 412
of the FD&C Act. Therefore, FDA is not making the changes requested in
this comment.
4. Administrative Procedures for Handling Notifications (Proposed Sec.
106.120(d), (e), and (f))
    Proposed Sec.  106.120 includes several subparts that address the
administrative aspects of new infant formula submissions. Specifically,
proposed Sec.  106.120(d) would have provided that a submission would
not constitute notice under section 412 of the FD&C Act unless the
submission complied fully with proposed Sec.  106.120(b) and was
readily understandable, and that FDA would notify the submitter of the
inadequacy of a submission. Proposed Sec.  106.120(e) would have
provided that FDA would acknowledge receipt of an adequate submission
and the date of receipt (``the filing date''), and restated the
prohibition against marketing the new infant formula until 90 days
after the filing date. Finally, proposed Sec.  106.120(f) would have
stipulated that if a manufacturer supplemented a new infant formula
submission, FDA would determine whether it was a substantive amendment,
and if so, the Agency would assign a new filing date and notify the
submitter of the new date.
    (Comment 331) One comment suggested that proposed Sec.  106.120(d)
be revised to require FDA to notify the submitter within 10 working
days if the submission is not complete because it

does not meet the requirements of sections 412(c) and (d) of the FD&C
Act. The comment asserted that manufacturers filing a new infant
formula submission need certainty for planning purposes, that an Agency
notice of inadequacy received well into the 90-day review period can be
seriously disruptive, and that a submission should receive immediate
review for completeness.
    (Response) FDA agrees that a new infant formula submission should
be checked immediately for completeness to ensure that it contains all
elements required under proposed Sec.  106.120(b). A submission lacking
any element required under proposed Sec.  106.120(b) will not be filed,
and the Agency will notify the submitter in a timely manner that the
submission is not complete. FDA would anticipate that this completeness
determination could generally be made within 10 business days. However,
given the constraints and conflicting demands on Agency resources at
various times, the Agency declines to add this time restriction to
Sec.  106.120(d).
    (Comment 332) One comment suggested that FDA delete the last
sentence of proposed Sec.  106.120(e), which would have stipulated that
a manufacturer not market a new infant formula until 90 days after the
filing date, because this language is not found in the FD&C Act and is
unnecessarily restrictive. The comment noted that the 1996 proposal
stated (61 FR 36154 at 36198) that the purpose of the 90 day notice is
to provide the Agency sufficient time to examine the submission and
decide whether there is any basis for concern about the marketing of
the formula, and, the comment contended, a manufacturer should not be
prohibited from marketing a formula if, prior to the 90th day, the
Agency has made its determination that there is no concern.
    (Response) FDA disagrees with this comment. Section 412(c)(1)(B) of
the FD&C Act states that no ``person shall introduce or deliver for
introduction into interstate commerce any new infant formula unless . .
. such person has at least 90 days before marketing such new infant
formula, made the submission to the Secretary required by subsection
(c)(1).'' \8\ The clear import of this provision is that a new infant
formula shall not be marketed until the passage of the 90 day period.
The statute does not require FDA to communicate with the submitter, and
the Agency, in its discretion, has chosen not to impose such an
obligation on itself because the requirement is unnecessary and would
be burdensome. In these circumstances, a manufacturer will know that
marketing of its new infant formula is lawful only with the passing of
the 90th day. FDA notes that, if the Agency's review of a new infant
formula submission uncovers deficiencies such that the new infant
formula in question would not be in compliance with the FD&C Act, the
Agency intends to notify the manufacturer of such deficiencies prior to
the 90th day. Accordingly, FDA declines to revise proposed Sec.
106.120(e) in response to this comment.
---------------------------------------------------------------------------

    \8\ FDA has previously stated the view that this reference to
subsection (c)(1) is a drafting error and is understood to refer to
subsection (d)(1)). (61 FR 36154 at 36195, footnote 6).
---------------------------------------------------------------------------

    (Comment 333) One comment suggested that proposed Sec.  106.120(e)
be revised to state that if a new infant formula submission is complete
and includes all information required by Sec.  106.120(b), FDA will
acknowledge its receipt and notify the submitter of the date of the
receipt. The comment expresses concern that the Agency might wish to
delay the starting date of the 90 day period when the notification is
complete but questions or disagreement remain with respect to the
content. The comment contended that the marketing of an infant formula
should not be deferred while the Agency takes issue with minor elements
of the notification and that when FDA receives a notification that
supplies information in accordance with Sec.  106.120, the 90-day clock
must begin to run.
    (Response) FDA stated in the response to Comment 331 that, in the
Agency's view, there is a distinction between verifying a submission's
completeness versus determining that the information satisfies the
requirements of the law and the relevant regulations by providing the
necessary assurances and demonstrating that the new infant formula will
not be adulterated under the FD&C Act. The latter determination
requires complete and careful examination of the submitted material by
Agency personnel with the necessary expertise, such as manufacturing
specialists, statisticians, microbiologists, nutritionists, food
technologists, and medical officers. In contrast, once the Agency
determines that a new infant formula submission is complete in that it
purports to address all the requirements of Sec.  106.120(b) of the
interim final rule, FDA intends to provide the submitter with a prompt
acknowledgement letter, and the 90 day period will begin as of the date
that the Agency receives a complete submission.
    In response to the foregoing comments, FDA is revising proposed
Sec.  106.120(e) to clarify the distinction between an FDA notification
that a submission is complete and a notification that the submission
does not provide the assurances required by section 412(d)(1) of the
FD&C Act and the regulations implementing those assurances.
    (Comment 334) One comment suggested that, in proposed Sec.
106.120(f), instead of referring to the ``manufacturer'' providing
additional information in support of a new infant formula submission
and FDA notifying the manufacturer of the new filing date, it would be
more appropriate to refer to the ``submitter'' providing additional
information and FDA notifying the ``submitter'' of the new filing date.
    (Response) FDA disagrees with the suggestion of this comment and,
for the reasons discussed below, is retaining the term ``manufacturer''
in Sec.  106.120(f) of the interim final rule. For purposes of
uniformity, the Agency is also revising Sec. Sec.  106.120(d),
106.130(c), and 106.140(c) by replacing the term ``submitter'' with
``manufacturer.''
    The manufacturer of an infant formula is ultimately responsible for
ensuring that that its formula products are lawful. In the case of a
new infant formula, FDA must be provided with all the information
required in a new infant formula submission at least 90 days before the
new formula is distributed in commerce. Thus, the formula manufacturer
must ensure that such information is provided in a timely fashion to
FDA. Also, section 412(c) of the FD&C Act refers to ``person'' and
requires such person to notify FDA of all establishments at which such
person intends to manufacture the new infant formula. Thus, ``person,''
as used in section 412(c) of the FD&C Act, refers to the manufacturer
of the infant formula.
    FDA recognizes that a manufacturer may contract with other entities
to execute certain aspects of formula production. However, the
manufacturer will be held responsible for the information submitted to
FDA, whether submitted by the manufacturer or another person who
submits it on behalf of the manufacturer, and FDA will notify the
manufacturer, under Sec.  106.120(f) of the interim final rule, whether
the Agency considers additional information submitted by any person on
behalf of the manufacturer in support of the submission to constitute a
substantive amendment resulting in a new filing date.
    For these reasons, FDA is retaining the term ``manufacturer'' in
Sec.  106.120(f) of the interim final rule, and, for consistency
reasons, is amending Sec. Sec.  106.120(d), 106.130(c), and

106.140(c) in the interim final rule by replacing the term
``submitter'' with the term ``manufacturer.''
    (Comment 335) One comment requested that FDA revise proposed Sec.
106.120(f) by adding a time period (5 working days) within which FDA
would acknowledge receipt of additional information provided to support
a new infant formula submission that is a substantive amendment to the
submission, asserting that FDA must be bound by some reasonable time
requirements so that manufacturers can plan appropriately.
    (Response) FDA agrees that the Agency should promptly notify a
manufacturer of receipt of a supplement to a new infant formula
submission, but the Agency declines to add a 5-day time limit to
proposed Sec.  106.120(f) within which to acknowledge such receipt. FDA
would anticipate that this acknowledgement could generally be made
within 5 business days. However, given the constraints and conflicting
demands on Agency resources at various times, the Agency declines to
add this time restriction or any other specific time restriction to
Sec.  106.120(f) in the interim final rule. There is no assurance that
FDA can meet this 5-day time limit given constraints that may be placed
on Agency resources at various times.
5. Submissions for Exempt Infant Formulas (Proposed Sec.  106.120(g))
    On its own initiative, FDA is adding Sec.  106.120(g) to the
interim final rule to clarify that the submission requirements for
exempt infant formulas are codified in 21 CFR 107.50. Section
106.120(g) of the interim final rule states: ``Submissions relating to
exempt infant formulas are subject to the provisions of Sec.  107.50 of
this chapter.'' The regulations in 21 CFR 107.50 pertaining to exempt
infant formula were finalized in 1985 (50 FR 48183) prior to the 1986
amendments. As explained in the 1996 proposal, the Agency will address
in a separate rulemaking the effect of the 1986 amendments on the
exempt infant formula regulations and exempt infant formulas (61 FR
36154 at 36201-36202). Until FDA publishes such rulemaking, exempt
infant formula submissions are subject to Sec.  107.50.

D. Quality Factor Submissions for Infant Formulas (Proposed Sec.
106.121)

    To provide assurance that an infant formula meets the quality
factor requirements set forth in subpart E, the proposed rule described
in detail the requirements for a quality factor submission in proposed
Sec.  106.121. The Agency received comments on these proposed
requirements, and responds below. Although much of the substance of
proposed Sec.  106.121 has been retained in the interim final rule, FDA
notes that the numbering of the section has been revised.
1. General Comments
    (Comment 336) One comment suggested that proposed Sec.  106.121 be
revised to clarify that the quality factor submission requirements of
proposed Sec.  106.121 only apply to ``new infant formulas'' as defined
by these regulations.
    (Response) FDA agrees with this comment. Under section 412(d)(1) of
the FD&C Act, any infant formula subject to section 412(c) must make a
submission to FDA. Each ``new infant formula'' is subject to section
412(c) of the FD&C Act. As such, FDA is making revisions to Sec.
106.121 in the interim final rule to clarify that the submission
requirements only apply to a ``new infant formula.'' The Agency notes,
however, that all infant formulas, whether new or ``not new,'' are
required to satisfy the applicable quality factor requirements of Sec.
106.96 of the interim final rule.
    (Comment 337) One comment recommended that Sec.  106.121(a) be
retained as proposed and that the remaining paragraphs in Sec.  106.121
applying to the quality factor of normal physical growth (proposed
Sec.  106.121(b), (c), (d), and (f)) be deleted for the reasons
identified in the comments objecting to establishment of ``normal
growth'' as a quality factor. The comment's support for retention of
proposed Sec.  106.121(a), as well as its support for deletion of Sec.
106.121(d), was contingent on FDA's acceptance of the comment's
suggested changes to proposed Sec.  106.120(b)(6)(i), (ii), and (iii).
Another comment on proposed Sec.  106.121 identified various changes to
infant formula and suggested a decision-tree approach to determining
the documentation that would be required for each such change to
support nutritional adequacy. The comment concluded that FDA should
provide information about presentation of clinical growth study data in
an Agency guidance and not the final rule.
    (Response) FDA disagrees with the comment that all information on
the presentation of growth monitoring study data should be incorporated
into an FDA guidance and not codified in Sec.  106.121. The data and
information required in a quality factor submission to assure normal
physical growth (proposed Sec.  106.121(b), (c), (d), and (f)) provide
the basic factual information that is needed for the Agency's review of
the growth monitoring study. Because these items are necessary to an
adequate review of the study, they should not, and cannot, be described
as optional elements of a submission. Therefore, FDA declines to delete
proposed Sec.  106.121(b), (c), (d), and (f), and these requirements
are, with minor editorial changes, incorporated into the interim final
rule recodified as Sec.  106.121(a)(2), (a)(3), (a)(4), and (h)
respectively. Proposed Sec.  106.121(a) is recodified as Sec.
106.121(a)(1) in the interim final rule, with minor editorial changes.
    Additional comments were submitted for proposed Sec.  106.121(b),
(c), and (f) and are addressed below.
2. Submission of Growth Data (Proposed Sec.  106.121(b))
    Proposed Sec.  106.121(b) would have required that a quality factor
submission include certain data from the growth monitoring study. FDA
received several comments that addressed the types of data that should
be submitted to comply with proposed Sec.  106.121(b).
    (Comment 338) One comment objected to submitting data for
individual subjects or a subgroup of individuals from a formula feeding
group. This comment expressed concern that, because few infants will be
at the lower or upper end of a particular growth parameter in a normal
distribution, the characteristics of these individuals could
erroneously be considered representative of a significant subgroup of
the sample. The comment requested that FDA clarify that group
statistics will provide the primary basis for the manufacturer's
finding that normal physical growth has been attained and that the
growth data for individual study infants will be considered as
supportive data and only to demonstrate that there was no significant
subgroup of the study group that experienced adverse effects.
    (Response) FDA declines to implement the suggestion of this
comment. Although the Agency intends to rely primarily on the group
data of a growth monitoring study to demonstrate the safety, including
the nutritional adequacy, of an infant formula, it has been the
Agency's experience that the review of summary data may raise issues
the resolution of which requires the consideration of individual or
subgroup data. For example, by examining detailed data, FDA has been
able to determine that there were no subgroups of the test population
for whom the formula had adverse effects. Thus, providing individual
subject data will facilitate FDA's review of the submission because the
Agency will be able to review individual data promptly and resolve
particular questions without

an intervening request to the manufacturer for additional data and
information. This efficiency is especially important given the limited
time (90 days) provided by the statute for the Agency's review of a new
infant formula submission. Accordingly, FDA is not persuaded to revise
the requirement of proposed Sec.  106.121(b), and this provision is
codified with minor editorial changes in the interim final rule as
Sec.  106.121(a)(2).
    (Comment 339) One comment suggested that growth data be presented
as plotted growth curves of the group means and that the Agency not
require individual case report forms and data. The comment pointed out
that including data on individual infants would add to the length of
the submission and to the length of the FDA's review without providing
a meaningful benefit to the public.
    (Response) FDA disagrees with this comment. As noted previously in
this document, the prompt availability of individual study results will
support the efficiency of FDA's review of the growth study and the
prompt resolution of issues identified by the Agency's review of the
group study results. Growth curves reflecting group means only may be
submitted but their submission is not an acceptable alternative for
submission of individual data. Importantly, FDA notes that in terms of
the form of individual study results, original records are not required
but may be submitted. In addition to the requirement to submit data
plotted on the 2009 CDC growth charts, manufacturers may submit such
information in any easily understandable format, which includes
spreadsheets, data tables, copies of investigators' original clinical
study records, or case report forms with original data (for example,
individual anthropometric data sheets). A submission form that contains
the individual subject data in an accessible format will satisfy FDA's
need for comprehensive information.
    (Comment 340) One comment requested that the preamble acknowledge
that the ``records'' contemplated by proposed Sec.  106.121(b) need not
be the investigator's original records, but could be records that
contain the necessary information drawn from the investigator's
original records.
    (Response) As noted in the response to the preceding comment, to
comply with Sec.  106.121(a)(2) of the interim final rule, a
manufacturer may submit the required information in any easily
interpretable format. Original records are not required to, but may, be
submitted to comply with Sec.  106.121(a)(2) of the interim final rule.
    (Comment 341) One comment on proposed Sec.  106.121(b) disagreed
with the requirement to submit the records that contain the information
required by proposed Sec.  106.97(a)(1)(ii).
    (Response) As discussed previously in this document in section
VIII.C, FDA is not finalizing the Agency's proposed recommendations for
a clinical study protocol in the interim final rule. However, not
issuing proposed Sec.  106.97(a)(1)(ii) in the interim final rule does
not change FDA's need to review the data and information that were
covered by proposed Sec.  106.121(b) to provide assurance that a new
infant formula meets the quality factor requirement of normal physical
growth. Thus, Sec.  106.96(b) of the interim final rule identifies the
data and other information that must be collected during a growth
monitoring study. FDA's reasons for retaining these substantive
requirements are discussed previously in this document in section
VIII.C. Accordingly, the Agency is not revising proposed Sec.
106.121(b) in response to this comment; the provision is recodified as
Sec.  106.121(a)(2) in the interim final rule with minor editorial
changes.
3. Statistical Power Calculations (Proposed Sec.  106.121(c)(2))
    Proposed Sec.  106.121(c)(2) would have required the quality factor
submission to include the calculation of the statistical power of a
study at its completion. FDA received several comments on this proposed
requirement.
    (Comment 342) One comment noted that a calculation of a study's
statistical power is needed before a study is initiated and it is
reasonable to expect from a study report that there was an a priori
calculation of the study's power, the number of subjects to be
recruited, and the number of subjects who actually completed the study.
The comment asserted that a calculation of a study's power at its
completion, as would have been required by proposed Sec.
106.121(c)(2), is unnecessary and of unproven value and could be a
confounding and burdensome calculation. Accordingly, the comment
recommended that FDA not require inclusion of such a calculation in a
quality factor submission.
    (Response) FDA agrees with this comment to the extent that it
asserts that the statistical power of a study should be calculated
prior to study initiation to determine the number of subjects needed to
answer the clinical question. It is both reasonable and reflects a
sound scientific approach for a manufacturer to perform a prospective
power calculation and include that calculation in a quality factor
submission relating to the growth monitoring study. A prospective power
calculation may be used to determine whether the study, as designed,
will have sufficient statistical power to answer the question of
whether a formula has the ability to satisfy the quality factor of
normal physical growth. Thus, the interim final rule requires a
manufacturer to calculate the statistical power of a growth monitoring
study prior to its initiation and to submit that calculation to FDA in
a new infant formula submission.
    The proposed rule would have required the calculation of the
statistical power of the growth monitoring study at its completion and
the inclusion of the calculation in the quality factor submission. A
prospective calculation of study power and sample size is based on
predicted variance and expected dropout rates whereas a power
calculation conducted at the end of a study uses actual values for the
study size and drop-out rates. As explained in the 1996 proposal (61 FR
36154 at 36199), a study may not achieve the power predicted by the
prospective power calculation if dropout rates or measurement errors
are greater than anticipated. Thus, an end-of-study calculation can
help determine whether the failure to detect a difference between
formulas occurred because the clinical study lacked the statistical
power to detect differences if such differences existed. Failure to
detect real differences could result in an erroneous conclusion that a
formula supports normal physical growth, when in fact, it does not.
Although post hoc analyses are generally discouraged, a planned, post-
study statistical power calculation is, in FDA's view, necessary to
ensure that the study, as actually conducted, achieved the statistical
power projected by the prospective statistical power analysis.
    FDA disagrees that a post-study power calculation is confounding
and burdensome. The data needed for these calculations are required to
be collected during the growth monitoring study, and the calculations
are straightforward and performed using standard statistical software
packages. For these reasons, the Agency is not deleting proposed Sec.
106.121(c)(2) in response to this comment.
    Based on the foregoing comments, the interim final rule requires
that the quality factor portion of a new infant formula submission
include both a prospective and a retrospective power calculation. Thus,
proposed

Sec.  106.121(c)(2) is included in this interim final rule as Sec.
106.121(a)(3)(ii) and states ``Calculations of the statistical power of
the study before study initiation and at study completion.''
4. Protein Quality (Proposed Sec.  106.121(e))
    Proposed Sec.  106.121(e) would have required that the quality
factor submission include the results of the PER study, consistent with
proposed Sec.  106.97(b). FDA received comments on this proposed
requirement.
    (Comment 343) One comment suggested that proposed Sec.  106.121(e)
be deleted and that the results of the PER be submitted to the Agency
after the first production, and before the introduction into interstate
commerce, of the new infant formula, as part of the verification
submission required by proposed Sec.  106.130. The comment further
suggested that proposed Sec.  106.130(b) be revised to require that the
verification submission include an assurance that the bioassay for
protein biological quality has commenced, and that the PER results will
be provided to FDA within 10 working days of their receipt by the
manufacturers or responsible party as a supplement to the verification
submission.
    The comment also asserted that if the use of new production
equipment triggers the 90-day premarket notification requirement, a
requirement to submit the PER testing in the 90-day premarket
submission would accelerate the need to start testing by 5 months (2
months to conduct the PER test plus three months to be able to give the
notification 90 days before marketing). This would delay the start-up
with the new equipment by 5 months or require the manufacturer to
convince FDA that the research production system was ``close enough''
to the full scale system so that the product of the former would be
viewed as representative of the latter.
    (Response) FDA is not persuaded by this comment to require the
submission of PER bioassay results as part of the verification
submission under Sec.  106.130. Nor is the Agency persuaded to require
that the verification submission only require an assurance that the
bioassay for protein biological quality was commenced, and that the
results will be forwarded to FDA within 10 working days of their
receipt by the manufacturer.
    Requiring the results of the PER bioassay to be submitted in a new
infant formula submission is consistent with both the relevant law and
sound science. As discussed previously in this document in section
VIII.E, FDA has established biological quality of the protein as a
quality factor for infant formula and has identified the PER bioassay
(appropriately modified) as the requirement that must be met to provide
assurance that this quality factor is satisfied. Section 412(d)(1) of
the FD&C Act requires that a new infant formula submission contain
assurances that the formula will not be marketed unless it satisfies
the quality factors established under section 412(b)(1) of the FD&C
Act. Indeed, in the 1996 proposal (61 FR 36154 at 36196), FDA
tentatively concluded that it would be appropriate to require the
assurance that the quality factors will be met by the submission of
data under proposed Sec.  106.120(b)(5)(i) and not as part of the
verification submission so that the Agency has all the information
relevant to the nutritional adequacy of the formula for a period of
time sufficient to conduct a meaningful review. Further, as discussed
previously in this document, it is appropriate that the biological
quality of a formula's protein component be established by the
manufacturer prior to initiation of a growth monitoring study to avoid
exposing infants to a test formula for which the protein quality has
not been confirmed. For these reasons, FDA concludes that it is
appropriate to require that the results of the PER assay be submitted
to the Agency as a part of the new infant formula submission made under
Sec.  106.120 of the interim final rule.
5. Certification Statement (Proposed Sec.  106.121(f))
    Proposed Sec.  106.121(f) would have required that a new infant
formula submission include a statement that certifies that the
manufacturer has collected and considered all information on the
ability of an infant formula to satisfy the quality factor requirements
and that the manufacturer is unaware of other information or data that
would show that the formula did not satisfy the quality factors
requirements. FDA received one comment on this provision.
    (Comment 344) One comment suggested a change to proposed Sec.
106.121(f). The comment requested that FDA change ``certifying'' to
``of assurance'' to reflect the language of section 412(d)(1)(C) and
(d)(1)(D) of the FD&C Act, which language refers to ``assurances'' and
not ``certifications.''
    (Response) FDA is not persuaded by this comment. The requirement
that a manufacturer include this certification in a quality factor
submission is a means of assuring FDA that the manufacturer has
considered the totality of available information and is not aware of
any information or data that would show that the formula does not meet
quality factor requirements. Therefore, FDA declines to revise proposed
Sec.  106.121(f) in response to this comment. Accordingly, proposed
Sec.  106.121(f) is recodified as Sec.  106.121(i) and is included in
this interim final rule as proposed.
6. Satisfaction of an Exemption From Certain Quality Factor
Requirements
    As discussed in section VIII.D, FDA is including exemptions from
the quality factor requirements in Sec.  106.96(b) and (f) as part of
this interim final rule (see Sec.  106.96(c) and (g) of the interim
final rule). A manufacturer may rely on an exemption, as applicable, in
a new infant formula submission to provide assurances that the formula
meets a quality factor requirement. Therefore, FDA is adding conforming
changes to Sec.  106.121 of the interim final rule to clarify the
requirements pertaining to each of these exemptions. To the extent a
manufacturer relies on an exemption in a new infant formula submission,
the applicable requirement in Sec.  106.121 of the interim final rule
would provide the Agency with the data and information in such
submission that the manufacturer relies on to demonstrate that the
formula satisfies such exemption from the quality factor requirements.

E. Verification Submissions (Proposed Sec.  106.130)

    In 1996, FDA proposed to implement section 412(d)(2) of the FD&C
Act by requiring that, after the first production, but before the
introduction into interstate commerce, of a new infant formula, a
manufacturer verify in a written submission to FDA that the formula
complies with the FD&C Act and is not adulterated. The proposal would
have required that the verification submission summarize test results
and records demonstrating that the formula satisfies the requirements
of section 412(b)(1), (b)(2)(A), (b)(2)(B)(i), (b)(2)(B)(iii),
(b)(3)(A), (b)(3)(C), and (i) of the FD&C Act.
    FDA received several comments on the proposed verification
requirement.
1. Scope of Verification Submission Requirement
    (Comment 345) One comment requested that FDA clarify that infant
formulas for export only are not required to submit a verification
submission under proposed Sec.  106.130.
    (Response) FDA agrees that clarification about how a manufacturer
of a new infant formula for export only can comply with Sec.  106.130
is needed.

The verification that must be submitted to FDA under section 412(d)(2)
of the FD&C Act relates to whether the formula is adulterated under
section 412(a) of the FD&C Act. As discussed previously in this
document, a manufacturer of a new infant formula for export only may
choose to comply with Sec.  106.120(c) of the interim final rule
instead of Sec.  106.120(b) of the interim final rule. If a
manufacturer complies with Sec.  106.120(c) of the interim final rule,
there would not be a need for the manufacturer of a product that is for
export only to submit a verification concerning compliance with