[Title 21 CFR 106]
[Code of Federal Regulations (annual edition) - April 1, 1996 Edition]
[Title 21 - FOOD AND DRUGS]
[Chapter I - FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES--CONTINUED]
[Subchapter B - FOOD FOR HUMAN CONSUMPTION]
[Part 106 - INFANT FORMULA QUALITY CONTROL PROCEDURES]
[From the U.S. Government Publishing Office]
21
FOOD AND DRUGS
2
1996-04-01
1996-04-01
false
INFANT FORMULA QUALITY CONTROL PROCEDURES
106
PART 106
FOOD AND DRUGS
FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES--CONTINUED
FOOD FOR HUMAN CONSUMPTION
PART 106--INFANT FORMULA QUALITY CONTROL PROCEDURES--Table of Contents
Subpart A--General Provisions
Sec.
106.1 Status and applicability of the quality control procedures
regulation.
106.3 Definitions.
Subpart B--Quality Control Procedures for Assuring Nutrient Content of
Infant Formulas
106.20 Ingredient control.
106.25 In-process control.
106.30 Finished product evaluation.
106.90 Coding.
Subpart C--Records and Reports
106.100 Records.
Subpart D--Notification Requirements
106.120 New formulations and reformulations.
Authority: Secs. 201, 412, 701 of the Federal Food, Drug, and
Cosmetic Act (21 U.S.C. 321, 350a, 371).
Source: 47 FR 17025, Apr. 20, 1982, unless otherwise noted.
Subpart A--General Provisions
Sec. 106.1 Status and applicability of the quality control procedures regulation.
(a) The criteria set forth in Secs. 106.20, 106.25, 106.30, 106.90,
and 106.100 shall apply in determining whether an infant formula meets
the safety, quality, and nutrient requirements of section 412 of the act
and the requirements of regulations promulgated under section 412(a)(2)
of the act.
(b) The failure to comply with any regulation set forth in
Secs. 106.20, 106.25, 106.30, 106.90, and 106.100 applicable to the
manufacturing, processing, and packaging of an infant formula shall
[[Page 175]]
render such formula adulterated under section 412(a)(1)(C) of the act.
(c) References in this part to regulatory sections of the Code of
Federal Regulations are to chapter I of title 21 unless otherwise noted.
Sec. 106.3 Definitions.
The definitions and interpretations contained in section 201 of the
act are applicable to such terms when used in this part. The following
definitions shall also apply:
(a) Indicator nutrient. An indicator nutrient is a nutrient whose
concentration is measured during the manufacture of an infant formula to
confirm complete addition and/or uniform distribution of a premix or
other substance of which the indicator nutrient is a part.
(b) In-process batch. An in-process batch is a combination of
ingredients at any point in the manufacturing process before packaging.
(c) Manufacturer. A manufacturer is a person who prepares,
reconstitutes, or otherwise changes the physical or chemical
characteristics of an infant formula and/or packages the product in a
container for distribution.
(d) Nutrient. A nutrient is any vitamin, mineral, or other substance
required in accordance with the table set out in section 412(g) of the
act or by regulations promulgated under section 412(a)(2)(A) of the act.
(e) Nutrient premix. A nutrient premix is a combination of
ingredients containing two or more nutrients. A nutrient premix either
may be received from a supplier or be prepared by an infant formula
manufacturer.
Subpart B--Quality Control Procedures for Assuring Nutrient Content of
Infant Formulas
Sec. 106.20 Ingredient control.
(a) Except as provided in Sec. 106.20(b), no analysis before use in
manufacturing is needed for ingredients that are generally stable in
shipping and storage, and that either are received under a supplier's
guarantee or certification that the mixture has been analyzed as to
nutrient composition or are labeled as having nutrient compositions
complying with specifications in the U.S. Pharmacopeia, the National
Formulary, the Food Chemicals Codex, or other similar recognized
standards.
(b) Unless each batch of finished product is analyzed as specified
in Sec. 106.30(b)(1) before release of product for commercial or
charitable distribution, the following shall apply:
(1) When an ingredient is relied upon as a source of a nutrient(s)
and when evidence indicates that such nutrient(s) in that ingredient is
likely to be affected adversely by shipping or storage conditions, the
manufacturer shall analyze that ingredient for each relied-upon nutrient
that may be affected, using validated analytical methods.
(2) Ingredients, including nutrient premixes, that are either
without a supplier's guarantee or certification, or not labeled as
complying with prescribed standards, shall be sampled and analyzed for
each relied-upon nutrient by the manufacturer, except that ingredients
used as a major source of protein or fat need not be analyzed for each
relied-upon nutrient if the manufacturer has records to show that each
relied-upon nutrient is present at a reasonably constant level. Nutrient
premixes prepared by the infant formula manufacturer shall be sampled
and analyzed for each relied-upon nutrient. Nutrient premixes which are
received from suppliers shall be sampled and analyzed for each relied-
upon nutrient unless the supplier has sampled and analyzed each batch of
premix for each relied-upon nutrient and has so certified in writing.
Sec. 106.25 In-process control.
(a) For each infant formula, a master manufacturing order shall be
prepared and approved by a responsible official of the manufacturer. The
manufacturer shall establish a quality control system that assures and
verifies the addition of each ingredient specified in the manufacturing
order.
(b) Unless each batch of finished product is analyzed as specified
in Sec. 106.30(b)(1), the manufacturer shall analyze each in-process
batch for:
(1) Solids;
(2) Protein, fat, and carbohydrates (carbohydrates either by
analysis or by mathematical difference);
[[Page 177]]
(3) The indicator nutrient(s) in each nutrient premix;
(4) Each nutrient added independently of nutrient premixes during
formulation of the product, except for linoleic acid, vitamin D, vitamin
K, choline, inositol, and biotin; and
(5) Solids or an appropriate nutrient to confirm proper dilution
when final dilution is made after performance of the analyses in
paragraph (b) (1) through (4) of this section.
Sec. 106.30 Finished product evaluation.
(a) The manufacturer shall establish criteria for sampling and
testing to ensure that each batch of infant formula meets the nutrient
requirements of section 412(g) of the act or of regulations promulgated
under section 412(a)(2) of the act before release of product for
commercial or charitable distribution.
(b)(1) Immediate analysis. Before release of product for commercial
or charitable distribution, the manufacturer shall analyze
representative samples of each batch of finished product for:
(i) Specific nutrient(s) to assess process degradation; and
(ii) All nutrients not previously analyzed for by the manufacturers,
unless each in-process batch is analyzed for nutrients as specified in
Sec. 106.25(b) and the ingredients are analyzed as specified in
Sec. 106.20(b). No analyses are needed for linoleic acid, vitamin D,
vitamin K, choline, inositol, and biotin; and for nutrients that are
added as a part of a nutrient premix analyzed by the manufacturer or
having a supplier's guarantee or certification and for which an
indicator nutrient(s) was analyzed by the manufacturer.
(2) Periodic analysis. The manufacturer shall sample at least one
newly processed finished product batch every 3 months and shall analyze
representative samples for all nutrients except those that the
manufacturers measured in the immediate analysis of that product batch.
(3) Stability analysis. Using representative samples collected from
finished product batches, the manufacturer shall conduct stability
analysis for selected nutrients with sufficient frequency to
substantiate the maintenance of nutrient content throughout the shelf
life of the product.
(c) The manufacturer shall evaluate new formulations and the effect
of changes in ingredients or processing conditions that could affect the
level of nutrients by means of a testing program designed to confirm
uniformity of batches and to determine the effects of such changes. The
following shall apply:
(1) A minor change is a minor reduction in nutrient levels, a minor
increase in levels of nutrients that are subject to maximum limits
established under section 412(g) of the act or in regulations
established under section 412(a)(2) of the act, or any other change
where experience or theory would not predict a possible significant
adverse impact on nutrient levels or nutrient availability. After a
minor change the manufacturer shall analyze representative samples for
all nutrients so changed and those possibly affected by the change.
(2) A major change is any new formulation, or any change of
ingredients or processes where experience or theory would predict a
possible significant adverse impact on levels of nutrients or
availability of nutrients. After a major change the manufacturer shall
analyze representative samples for osmolality, all nutrients, and the
biological quality of the protein. A protein biological quality analysis
is not necessary for a formulation change that is not expected to have
an adverse effect on the biological quality of the protein. Vitamin D
shall be determined by the rat bioassay method as prescribed in
``Official Methods of Analysis of the Association of Official Analytical
Chemists'' (AOAC), 13th Ed. (1980), sections 43.195-43.208, ``Vitamin D
(30)--Official Final Action,'' which is incorporated by reference.
Copies are available from the Association of Official Analytical
Chemists, 2200 Wilson Blvd., Suite 400, Arlington, VA 22201-3301, or
available for inspection at the Office of the Federal Register, 800
North Capitol Street, NW., suite 700, Washington, DC. Before release of
the product for commercial or charitable distribution, the manufacturer
shall have completed all appropriate analyses except that shipment of
the product need not be
[[Page 178]]
delayed until results of the vitamin D bioassay and, if required, a
protein biological quality bioassay are complete, provided such
bioassays have been initiated, and if another analysis for the vitamin D
has been run and the protein content has been determined by a suitable
method. The biological quality of the protein shall be determined by an
appropriate modification of the AOAC bioassay method of analysis. The
manufacturer shall analyze additional samples from the same batch for
vitamin D, by any suitable method, and for the biological quality of the
protein. The manufacturer shall perform such analyses at least annually
for a period not to exceed the expected shelf life of the product.
(d) A simple adjustment in the level of an ingredient to accommodate
inconsistencies in processing is considered to be neither a minor nor a
major change.
[47 FR 17025, Apr. 20, 1982, as amended at 54 FR 24891, June 12, 1989]
Sec. 106.90 Coding.
The manufacturer shall code all infant formulas in conformity with
the coding requirements that are applicable to thermally processed low-
acid foods packaged in hermetically sealed containers as prescribed in
Sec. 113.60(c).
Sec. 106.100 Records.
(a) Every manufacturer of infant formula shall maintain the records
specified in this regulation in order to permit the Food and Drug
Administration to determine whether each manufacturer is in compliance
with section 412 of the Federal Food, Drug, and Cosmetic Act (the act).
(b) The manufacturer shall maintain all records that pertain to
food-packaging materials subject to Sec. 174.5 of this chapter and that
bear on whether such materials would cause an infant formula to be
adulterated within the meaning of section 402(a)(2)(C) of the act.
(c) The manufacturer shall maintain all records that pertain to
nutrient premix testing that it generates or receives. Such records
shall include, but are not limited to:
(1) Any results of testing conducted to ensure that each nutrient
premix is in compliance with the premix certificate and guarantee and
specifications that have been provided to the manufacturer by the premix
supplier, including tests conducted when nutrients exceed their
expiration date or shelf life (retest date).
(2) All certificates and guarantees given by premix suppliers
concerning the nutrients required by section 412(i) of the act and
Sec. 107.100 of this chapter.
(d) The premix supplier shall maintain the results of all testing
conducted to provide all certificates and guarantees concerning nutrient
premixes for infant formulas. Such records shall include but are not
limited to:
(1) The results of tests conducted to determine the purity of each
nutrient required by section 412(i) of the act or Sec. 107.100 of this
chapter and any other nutrient listed in the certificate and guarantee;
(2) The weight of each nutrient added;
(3) The results of any quantitative tests conducted to determine the
amount of each nutrient certified or guaranteed; and
(4) The results of any quantitative tests conducted to identify the
nutrient levels present when nutrient premixes exceed their expiration
date or shelf life (retest date).
(e) The manufacturer shall maintain all records necessary to ensure
proper nutrient quality control in the manufacture of infant formula
products. Such records shall include the results of any testing
conducted to verify that each nutrient required by section 412(i) of the
act or Sec. 107.100 of this chapter is present in each batch of infant
formula at the appropriate concentration. This requirement pertains to
ingredients, in process batch and finished product from the time of
manufacture through its expiration date.
(f) The manufacturer shall maintain all records necessary to ensure
required nutrient content at the final product stage. Such records shall
include, but are not limited to, testing results for vitamins A, B1
(thiamine), C, and E for each batch of infant
[[Page 179]]
formula. ``Final product stage'' means the point in the manufacturing
process prior to distribution at which the infant formula is homogenous
and not subject to further degradation from the manufacturing process.
(g) The manufacturer shall maintain all records pertaining to
distribution of the infant formula. Such records shall include, but not
be limited to, all information and data necessary to effect and monitor
recalls of the manufacturer's infant formula products in accordance with
subpart E of part 107 of this chapter.
(h) The manufacturer shall maintain all records pertaining to the
microbiological quality and purity of raw materials and finished
powdered infant formula.
(i) [Reserved]
(j) The manufacturer shall maintain all records pertaining to
regularly scheduled audits, including audit plans and procedures. Audit
plans identify the specific manufacturing and quality control procedures
to be reviewed. Audit procedures are the methods used to review the
manufacturing and quality control procedures. Records of audits shall
include the information and data necessary for a determination as to
whether the manufacturer complies with the current good manufacturing
practices and quality procedures identified in parts 106, 107, 109, 110,
and 113 of this chapter. The records shall include written assurances
from the manufacturer that regularly scheduled audits are being
conducted by appropriately trained individuals who do not have any
direct responsibility for the manufacture or production of infant
formula, and that the complete audit plans and procedures for the firm
have been followed. The actual written reports of the audits need not be
made available.
(k) The manufacturer shall maintain procedures describing how all
written and oral complaints regarding infant formula will be handled.
The manufacturer shall follow these procedures and shall include in them
provisions for the review of any complaint involving an infant formula
and for determining the need for an investigation of the possible
existence of a hazard to health.
(1) For purposes of this section, every manufacturer shall interpret
a ``complaint'' as any communication that contains any allegation,
written or oral, expressing dissatisfaction with a product for any
reason, including concerns about the possible existence of a hazard to
health and about appearance, taste, odor, and quality. Correspondence
about prices, package size or shape, or other matters that could not
possibly reveal the existence of a hazard to health shall not, for
compliance purposes, be considered a complaint and therefore need not be
made available to an FDA investigator.
(2) When a complaint shows that a hazard to health possibly exists,
the manufacturer shall conduct an investigation into the validity of the
complaint. Where such an investigation is conducted, the manufacturer
shall include in its file on the complaint the determination as to
whether a hazard to health exists and the basis for that determination.
No investigation is necessary when the manufacturer determines that
there is no possibility of a hazard to health. When no investigation is
necessary, the manufacturer shall include in the record the reason that
an investigation was found to be unnecessary and the name of the
responsible person making that determination.
(3) When there is a reasonable possibility of a causal relationship
between the consumption of an infant formula and an infant's death, the
manufacturer shall, within 15 days of receiving such information,
conduct an investigation and notify the agency as required in
Sec. 106.120(b).
(4) The manufacturer shall maintain in designated files all records
pertaining to the complaints it receives. The manufacturer shall
separate the files into two classes:
(i) Those complaints that allege that the infant became ill from
consuming the product or required treatment by a physician or health-
care provider.
(ii) Those complaints that may involve a possible existence of a
hazard to health but do not refer to an infant becoming ill or the need
for treatment by physician or a health care provider.
[[Page 180]]
(5) The manufacturer shall include in a complaint file the following
information concerning the complaint:
(i) The name of the infant formula;
(ii) The batch number;
(iii) The name of complainant;
(iv) A copy of the complaint or a memo of the telephone conversation
or meeting and all correspondence with the complainant;
(v) By reference or copy, all the associated manufacturing records
and complaint investigation records needed to evaluate the complaint.
When copies of such records are not maintained in the complaint file,
they must be available within 24 hours when requested by an FDA
official.
(vi) All actions taken to follow up on the complaint; and
(vii) All findings and evaluations of the complaint.
(6) The manufacturer should maintain the files regarding infant
formula complaints at the establishment where the infant formula was
manufactured, processed, or packed. When the manufacturer wishes to
maintain all consumer complaints for the entire firm at one location
other than at the facility where an infant formula was manufactured,
processed, or packed, the manufacturer may do so as long as all records
required by this section are available within 24 hours of request for
inspection at that facility. However, all records of consumer
complaints, including summaries, any reports, and any files, maintained
at the manufacturing facility or at any other facility shall be made
available to investigators for review and copying upon request.
(l) The manufacturer shall make readily available for authorized
inspection all records required under this part or copies of such
records. Records shall be available at any reasonable time at the
establishment where the activities described in such records occurred.
(Infant formula complaint files may be maintained at one facility, as
provided in Sec. 106.100(k)(6), if all required records are readily
available at that facility.) These records or copies thereof shall be
subject to photocopying or other means of reproduction as part of such
inspection. Records that can be immediately retrieved from another
location by electronic means shall be considered as meeting the
requirements of this paragraph.
(m) Records required under this part may be retained either as
original records or as true copies such as photocopies, microfilm,
microfiche, or other accurate reproductions of the original records.
Where reduction techniques, such as microfilming are used, suitable
reader and photocopying equipment shall be readily available.
(n) Production control, product testing, testing results,
complaints, and distribution records necessary to verify compliance with
parts 106, 107, 109, 110, and 113 of this chapter, or with other
appropriate regulations, shall be retained for 1 year after the
expiration of the shelf life of the infant formula or 3 years from the
date of manufacture, whichever is greater.
(o) The manufacturer shall maintain quality control records that
contain sufficient information to permit a public health evaluation of
any batch of infant formula.
[56 FR 66571, Dec. 24, 1991; 57 FR 7435, Mar. 2, 1992]
Subpart D--Notification Requirements
Sec. 106.120 New formulations and reformulations.
(a) Information required by section 412(b)(2) and (3) of the act
shall be submitted to Center for Food Safety and Applied Nutrition (HFS-
450), Food and Drug Administration, 200 C St. SW., Washington, DC 20204.
(b) The manufacturer shall promptly notify the Food and Drug
Administration when the manufacturer has knowledge (as defined in
section 412(c)(2) of the act) that reasonably supports the conclusion
that an infant formula that has been processed by the manufacturer and
that has left an establishment subject to the control of the
manufacturer may not provide the nutrients required by section 412(g) of
the act and by regulations promulgated under section 412(a)(2) of the
act, or when there is an infant formula that is otherwise adulterated or
misbranded and that may present risk to human health. This notification
shall be made, by telephone, to the Director of the
[[Page 181]]
appropriate Food and Drug Administration district office specified in
Sec. 5.115. After normal business hours (8 a.m. to 4:30 p.m.) the FDA
emergency number, 202-737-0448, shall be used. The manufacturer shall
send a followup written confirmation to the Center for Food Safety and
Applied Nutrition (HFS-605), Food and Drug Administration, 200 C St.
SW., Washington, DC 20204, and to the appropriate Food and Drug
Administration district office specified in Sec. 5.115.
[47 FR 17025, Apr. 20, 1982, as amended at 54 FR 24891, June 12, 1989;
61 FR 14479, Apr. 2, 1996]